Brachytherapy: Applications and Technique, 1st Edition

3. Head and Neck Brachytherapy


Peter Han

Kenneth S. Hu

Ravi A. Shankar

Louis B. Harrison

Brachytherapy is an important option in the armamentarium of a radiation oncologist treating head and neck squamous cell cancer. It involves the implantation of radioisotopes into tumors to allow high dose conformality with dose intensification to areas of high volume disease and rapid inverse square falloff to the surrounding normal tissue. It can play an integral role in organ and function sparing strategies, which can maximize a patient's quality of life functionally, psychologically, and cosmetically.

Brachytherapy can be divided into multiple categories: Interstitial, intracavitary, intraluminal, and surface applicator techniques. In addition, the application can be further subdivided depending upon the loading technique (preloading or afterloading), the dose rate (low dose rate [LDR] or high dose rate [HDR]), and duration of the implant (temporary or permanent). In interstitial brachytherapy, the radioisotope is placed either temporarily or permanently into the tumor site or bed. Intracavitary or intraluminal brachytherapy entails temporary application in a natural cavity near the tumor bed. Surface application has been more commonly applied intraoperatively after a gross total resection to the exposed tumor bed while shielding adjacent normal tissues.

Brachytherapy can be administered as a single modality or as boost treatment in combination with external beam radiation therapy (EBRT) to treat cancers definitively or adjuvantly.1,2,3,4,5 In advanced cancers, brachytherapy may be used in various combinations and strategies with EBRT, chemotherapy, and surgery.6,7 When used as the sole modality, brachytherapy may preserve the option of EBRT for possible future lesions that may develop. In patients previously treated with EBRT, brachytherapy can be a pivotal part of the radiation therapy (RT) for patients with recurrent disease.

Although there are no phase III prospective randomized double-blind trials comparing brachytherapy with conformal fractionated EBRT in any select group of patients with head and neck malignancies, there are many decades of clinical experience supporting the implementation of brachytherapy as part of the optimal treatment strategy for various head and neck sites.8,9,10,11 In the era of organ sparing approach, the ultimate treatment goal would be to provide optimal cure rate and quality of life.

Given the complex anatomy of the head and neck region, the excellent results obtained with brachytherapy can be attributed to the training, skill, technique, and experience of the brachytherapist. These techniques are ideally performed by the radiation oncologist in centers with a large patient volume, well-trained physicists, a highly functional multidisciplinary team of head and neck surgeons, plastic surgeons, radiologists, dental surgeons, a pain management team, speech and swallowing rehabilitation specialists, social workers, and dedicated and knowledgeable nursing staff.


Brachytherapy as a mode of cancer treatment is as old as the history of RT itself.12 The prefix for brachytherapy is derived from the Greek word ‘brachy’, which means ‘short’. The application refers to the use of sealed radioisotopes near or within the tumor volume. The history of RT reveals the remarkable short interval between a scientific discovery and its potential clinical applications. In 1895, Wilhelm Roentgen discovered x-rays while working with a cathode-ray tube. This new type of radiation was able to travel through objects including a human body, producing photographs of a person's bones. Soon after the discovery, a French physicist, Henri Bequerel, discovered that uranium emitted invisible rays after exposing photographic film. In 1898, Marie Curie coined the term radioactivity to explain the emitted rays in addition to the discovery of radium. With the discovery of radium, its potential clinical application became apparent. Pierre Currie (Marie Curie's husband and colleague) suggested a small radium tube be inserted into a tumor, thereby inventing the concept of brachytherapy.13 In 1903, Henri Bequerel, Marie, and Pierre Curie were awarded the Nobel prize for their discoveries. In the same year, Alexander Graham Bell suggested that a tiny fragment of radium sealed in a fine glass tube could be inserted into the very heart of the cancer site.14 The earliest applications were crude devices of capsules of radioactive material placed over the skin. In 1904, Wickham and Derais used sharpened goose quills to perform intratumoral implantations.15 Abbe and Morton have reported anecdotal reports of cure for cancers in the head and neck.16,17 In 1909, Minet described the first use of a radium tube placed in a catheter to treat prostate cancer.18

With the discovery of radium isotope, the clinical applications and experience were rapidly expanding. Radium, which has a half-life of 1,600 years, disintegrates to form radon. Through its complex decay scheme, γ rays of different energies ranging from 0.05 to 2.4 MeV are emitted with an average energy of 0.8 MeV.19 The unit of activity, called curie, was defined as the rate of nuclear disintegration of 1 g of radium. Because radium provided the foundation of brachytherapy, the measured outputs of future isotopes were based in comparison to an equivalent 1 mg of radium called milligram radium equivalent (mgRaEq) and the dose was in mgRaEq-hr. However, before the computer era, a system of dose calculations and distributions was needed. In the 1930s, Ralston Paterson and Herbert Parker devised a method for implantation of radioactive sources, to permit a uniform dose distribution thought the target volume.20 Their rules, also called the Paterson-Parker system or the Manchester system, helped obtain a more uniform dose homogeneity within a volume or planar implant. Because of the dose falloff characteristics from a radioactive source secondary to the inverse-square law, their system of implant distribution designates a higher peripheral radioactivity implant in comparison to the center, ultimately delivering a dose to the planar or volume implant with a ± 10% dose distribution. Another historical approach was developed by Edith Quimby of Memorial Sloan-Kettering in New York, which included a system of tables and rules in relation to the placement of sources in a uniform grid, achieving higher doses at the center in comparison to the periphery of the tumor.21,22 Unlike the Manchester system, the Quimby system would describe sources of equal linear activity spaced in a uniform manner, resulting in a greater central dose distribution as compared with the periphery.21,22,23 Paris system is another set of rules for implantation used mainly for temporary iridium 192 (192Ir) wires.24,25 When uniform linear parallel sources were used, the rules resulted in a reference isodose that covered the treatment target volume. The reference isodose is 85% of the average basal dose, which is defined by the minimum dose between the sources. In the modern era with the advent of computers, imaging technologies, dose-calculating algorithms, the radiation treatment planning has considerably evolved to aid in optimal and accurate radiation delivery.

With the discovery of artificial radionuclides, a new era developed in brachytherapy. These new radioactive sealed sources were safer, in addition to allowing them to be molded and fashioned in useful ways. 192Ir seeds and ribbons in plastic catheters were used for implanting tumors. In the 1960s, Henshke et al. introduced the ingenious afterloading technique (in comparison to preloading, where radioactive sources are implanted during the initial procedure), where the sources were inserted into the previously implanted applicators or catheters within the tumor, minimizing the potential exposure of radiation to medical personnel.26,27Over the years, dedicated physicians and research, greater sophistication and innovations of application techniques, improvement in dosimetry planning, and stringent quality control measures have made brachytherapy an effective and integral radiation treatment technique, providing “the ultimate conformal radiation therapy.”

Basic Principles

Patient Selection

The appropriate application of brachytherapy begins with the proper selection of patients. Patients with medical comorbidities that have contraindications for surgery may be poor candidates for brachytherapy. In addition, patients with alcohol dependencies, major neurologic deficits, poor cardiopulmonary status, memory disorders, and hematologic disorders may also not be ideal candidates. Age alone is not a contraindication. In addition to various medical conditions, patients must also be assessed for their understanding and ability to comply with the necessary inherent radiation precautions and procedures associated with brachytherapy implants, especially for LDR implants. Patients must be able to provide baseline self care needs during the radiation delivery. This can include care to the tracheostomy, self-administered feeds through percutaneous endoscopic gastrostomy tube or nasogastric tube, and a patient-controlled analgesic pump, as indicated. Patients with periods of confusion and disorientation would not be ideal candidates. The potential for alcohol or narcotic withdrawal should be addressed to avoid complications with the delivery of the implant. The evaluation for patient selection also includes appropriateness of a brachytherapy implant regarding the tumor location, size, extent of tumor volume, and organ function. Additional patient-related factors associated with severe soft tissue and bone complications after an implant include severe diabetes, liver failure, and compromised arterial status.28

In addition to patient education and assessment, evaluation of the patient's oral/dental hygiene is also necessary, especially with regard to risk of mandibular osteoradionecrosis. Examination by a dentist or oral surgeon familiar with RT is an integral part of initial evaluation for brachytherapy for a subset of patients. Patients must be able to tolerate a custom-designed mandibular shield in the oral cavity during the radiation delivery as protection against osteoradionecrosis (see Fig. 3.1).29

Figure 3.1 A custom-designed dental shield lined with lead. A dental cast is used to make the shield. (Courtesy of Louis B. Harrison, M.D.).


Radioisotope Selection and Implant

Historically, radium 226 (226Ra) and radon 222 (222Rn) sources were mostly used in brachytherapy. However, now there are various radioisotopes that are commercially available for clinical use and are artificially manufactured. Some of the clinically used isotopes in brachytherapy include iridium 192 (192Ir), iodine 125 (125I), cobalt 60 (60Co), cesium 137 (137Cs), gold 198 (198Au), and palladium 103 (103Pd). The tumor size, location, geometry, organ motion, and proximity of surrounding critical structures, in addition to the brachytherapist's experience, will influence the overall technique and approach to the brachytherapy. The proper selection should enable the appropriate planning and preparation for a successful implant.

An initial step would be to determine whether a permanent implant or a temporary implant should be used. In permanent implants, a radioisotope is implanted into the tumor site, emitting low dose of radiation over the lifetime of its radioactivity. A permanent implant may be advantageous when the target volume is irregular and complex, making temporary catheter placement impractical and avoiding situations that result in potential kinking of the catheters. In addition, a permanent implant allows for a higher total radiation dose to be delivered to the target volume.

A commonly used radioisotope for permanent implants is 125I. This source has a half-life of 60.2 days and decays by electron capture, resulting ultimately in photons with an overall mean energy of 28 keV4. In addition to reduction of radiation exposure to personnel, 125I may be advantageous when critical normal structures, such as the spinal cord, are adjacent to the tumor implant. Depending upon the requested activity of the sources, 125I can also be used for temporary implants, which may be ideal because of the rapid falloff for certain situations.30 Other isotopes used in permanent implants include 103Pd and 198Au.

Temporary implants are more commonly used in head and neck cancer. As discussed earlier, there are several categories of temporary brachytherapy. The more commonly used approach includes interstitial implant, where the sources are loaded through implanted catheters into the tumor volume. This application system allows for a more deliberate and accurate placement without the risk of radiation exposure that is associated with permanent implants during implantation. In addition, the implant dosimetry can then be optimized using various planning systems with three-dimensional (3D) reconstruction of the implant geometry. This is commonly done using orthogonal x-rays of the implant with dummy seeds placed within the selected applicator system. The dummy seeds will provide the relative seed positions in the implant. Variations in the activity, the number of radioactive sources, and the loading duration, in addition to variations in dwell time and position for a high dose rate computer-guided remote afterloading system, will allow for optimization of the implant dosimetry. However, even the best optimization cannot overcome a poorly implanted system.

The most commonly used temporary radioisotope is 192Ir. This source has a half-life of 74.2 days and undergoes β decay emitting polyenergetic γ rays with a mean energy of 380 keV4192Ir sources are available as seeds that are encapsulated in either platinum or steel and are available in a nylon ribbon or in the form of a thin wire. The seeds are placed 1 cm apart, with center-to-center intervals. The usual strengths of 192Ir seeds are in the range of 0.3 to 1.0 mgRaEq.


A successful brachytherapy requires meticulous placement of radioactive sources in the planned tumor volume. Knowledge regarding the extent of tumor from palpation and inspection of the disease, prior radiologic examination, awareness of adjacent critical structures, any prior radiation exposure, and relationship of the tumor to the surrounding structures are of utmost importance for optimal and safe placement of the radioactive sources. There are various techniques with many modifications over the years. Currently, most interstitial head and neck implants are based on an afterloading system with a computerized treatment planning system. Some of the main interstitial techniques used in photon emitting implants will be discussed.31


Pierquin and Chassagne Guide Gutter or Hairpin Technique

This approach uses hairpins of various sizes consisting of two parallel branches, which provide rigid guides to facilitate the implantation of iridium wires into the tumor. The guide materials are either twin or single guide gutters made of stainless steel. Once the iridium has been implanted, the gutter guides would then be removed, resulting in a predictable implant geometry. This technique is used in anatomic sites within the head and neck region, particularly when the tumor volumes are small to moderate.

Plastic Tube Technique of Henschke

This is one of the most popular techniques with various modifications. In this technique, rigid metal hollow guide needles are implanted into the tumor volume by free hand. The placement and spacing can be verified by visualization, ultrasound guidance, or under fluoroscopy. Plastic tubes are then threaded into these rigid hollow needles and left in place to cover the entire target volume with subsequent removal of the metal needles. The plastic tubes are secured in close proximity to the skin with metallic buttons. Radioactive sources are then afterloaded into these plastic tubes following dosimetry planning. Many variations exist including the pushing method of substitution and Raynal's pulling method of substitution. The latter is an excellent technical method for loops within the tumor volume and is commonly used in base of tongue brachytherapy implants. Large tumors are effectively treated with this approach.

Hypodermic Needle Technique of Pierquin

Hypodermic needles, beveled at both ends, are implanted into the tumor volume and then transfixed to the skin at either end. This technique with various modifications is used when both sides of the tumor are accessible for implant. 192Ir wires are then threaded into the hollow needles so that only a small segment protrudes on both ends. Spacing material is then slipped into the ends, and lead caps are crimped into place. This technique is especially useful in tumors of the lip (see Fig. 3.2).

Thread Technique

Radioactive sources are braided onto a suture material. The sutures are then sewn into the target volume in its desired positions. A modification of this technique includes threading the suture seeds into a mesh, which is then secured over the tumor bed.

Direct Implantation Method

The radioactive sources are directly implanted permanently into the planned target volume. A specialized applicator would be used to facilitate the implant. This requires meticulous planning and radiologic guidance for accurate placement of the seeds to achieve good geometry and dose distribution.

Figure 3.2 An illustration of an implant for a small lip cancer using the hypodermic needle technique of Pierquin.

Depending upon the insertion and catheter orientation in relation to the implant volume, another set of general techniques based on the plastic tube technique is considered.

Through-and-through Technique

This approach is mainly suited for tumor volumes when both sides are accessible for implantation. The various tumor sites include the lips, buccal mucosa, skin and neck nodes. The first step is the identification of the intended implant tumor or target volume and the point of entries for the brachytherapy catheters. This ensures that the implanted catheters will align in parallel and cover the site of disease. This step can be facilitated with the use of surgical marker delineating the disease and catheter entry points, with catheter spacing approximately 1-cm apart. Using a metal needle or trocar, the skin is pierced at the planned entry site and coursed along in the tumor volume, exiting at the marked skin site at the other end of the target volume. Once in place, a nylon afterloading catheter is threaded through the trocar, exiting on the other end of the trocar. The catheter is then adjusted such that the wider portion of the afterloading catheter encompasses the target volume. The trocar is then removed along its original pathway while holding the implanted catheter in place. A metal button along with a half-moon-shaped plastic button is then threaded over the exposed ends of the catheter and crimped in placed over the skin entry sites. Silk ties can then be sutured to the skin through the available holes in the button for further stabilization. The exposed end of the catheter is then cut off leaving at least several centimeters distal to the metal button. These series of steps would then be repeated, resulting in a parallel distribution of catheters expanding the tumor volume. Depending upon the site, patient's cormobidities, and extent of implant, the procedure can be done under local or general anesthesia.

Loop Technique

This approach has technical aspects that are similar to the through-and-through technique. However, the catheters will be exiting along the same side of the entry points, resulting in a looping of the catheters. This technique is most commonly used for oral cavity and oropharyngeal sites.33,34 Because this is commonly done for a tongue implant, the technique will be discussed for such an implant. After identification of the planned target volumes, critical adjacent normal structures should be delineated with a surgical marker, which include the carotid and facial artery in addition to the hyoid bone. Once the target volume has been assessed, the overall strategy for implantation should be planned out regarding the number of catheters, orientation, placement, and their entry/exit sites. A curved metal trocar is then inserted through the submental region traversing through the site of disease and exits out of the tongue. An afterloading catheter is then threaded through the metal trocar and out of the mouth. The catheter is then held in place as the metal trocar is removed along its original entrance pathway. A similar insertion is then performed with curved metal trocar adjacent to the prior entry point and exiting out of the tongue approximately 1.0 cm away from the prior exiting point. The previous catheter is then looped back and threaded through the adjacent trocar until the catheter's end is appreciated at the other end. While securing the catheter, the trocar is then carefully removed. The exposed ends of the catheters are then secured using metal buttons. Sutures are typically not necessary to secure the position. These various steps would be repeated, resulting in a set of looped catheters in multiple planes covering the target volume. Typically, each plane is approximately 1 cm from the others.

Sealed End Technique

In contrast to the through-and-through technique, the catheters exit through only a single side of the implanted target volume. This technique is more commonly utilized outside the head and neck region, typically under situations when it is not pragmatic to have the catheters exit through both sides of an implant target volume. After identification and delineation of skin entry points and target volume, metal trocars are percutaneously inserted into the tumor site. An afterloading catheter is then threaded through the trocar and over the target volume, which can include a tumor bed with margin. After retraction of the trocar, absorbable sutures are used to tie the catheter in place at various intervals to stabilize its position. This step is then repeated, resulting in a parallel distribution of the catheters over the target volume. Typically, the catheters are approximately 1 cm apart in a single plane implant and 1.2 cm in a multiplane implant and 1.5 cm apart from each plane. Each of the catheters would then be secured using a metal and half-moon-shaped buttons crimped and sewn into place over the entry point.

Typically, the temporary implant procedure is done free hand although techniques using templates are available. With each approach, various instruments are needed to facilitate the implant. These may include the following (see Fig. 3.3):

1. A nylon afterloading flexible catheter 60-cm long with a thin leader portion with an inner wire to prevent kinking of catheter

2. A curved or a straight stainless steel trochar

3. Metal buttons to secure the end of the catheter and the containing sources after crimping with holes on the button that allow suturing to the adjacent skin for added secure placement

4. Crimper

5. Plastic half-moon-shaped buttons to separate the metal button from the skin, preventing electron scatter from the metal buttons

6. A 15-cm stainless steel ruler

7. Radiopaque dummy sources spaced 1 cm apart with various different identification schemes to help differentiate between multiple catheters

Figure 3.3 Various instruments for a brachytherapy implant. A: Nylon afterloading catheters. B: Metal buttons. C: Half-moon-shaped buttons. D: Stainless steel curved trocar. E: 15-cm stainless steel ruler. F: Crimper. G: Dummy sources.


High dose rate versus Low dose rate Brachytherapy

Some of the many advances in radiation oncology have been through the development of innovative and technologic achievements in the delivery of radiation. The miniaturization of high-activity radioisotopes along with sophisticated computer technology has led to the establishment of remote afterloading HDR brachytherapy. The afterloading concept was introduced by Henschke and minimizes the potential radiation exposure during an implantation procedure.28,29The International Commission on Radiation Units and Measurements Report #38 defined LDR as radiation dose delivered at 0.4 to 2.0 Gy per hour and HDR of >12.0 Gy per hour.35 HDR afterloading system consists of a computer-guided remote source afterloading machine, 192Ir source, transfer tubes/applicators, a computer treatment planning system, and a control console (see Figs. 3.4 and 3.5). Fractionated high-dose RT can be delivered with a single high activity 192Ir source that is fixed to the end of a computer-controlled sliding guide wire through a transfer tube into the placed applicator/catheter. The source then positions itself for a predetermined length of time at various dwell positions that are 5-mm apart. Depending upon the dwell time calculated by the treatment planning system, each position can be emitting various amounts of radiation dose, enabling significant conformal isodose coverage of the target volume.

In comparison, the advantages with LDR include a continuous exposure of the cancer cells exploiting the cell cycle–specific radiosensitization, a reduced adverse influence of hypoxia, decreased risk of late normal toxicity, and increased repair capacity of normal tissues. However, the advantages of HDR compared with LDR are greater enhanced ability to conform the implant dosimetry to the target volume, decreased risk of radiation exposure for medical personnel, and better dose distribution homogeneity within the target volume with potential for less normal tissue irradiation. In addition, because of the decreased radiation delivery time, there is less likelihood of organ movement and higher likelihood of treating the patient as an outpatient. However, because of the differences in radiation biologic effect of high dose per fraction, there are some concerns remaining regarding the risk of increased late complications.36 There has been a growing reported experience with the use of HDR in the head and neck population.37,38,39,40 Local control rates are as good as those obtained by LDR. Inoue et al. reported on a phase III trial of HDR versus LDR for early mobile tongue cancer, revealing similar local and regional control.39 Kakimoto and Inoue et al. also reported, in a retrospective analysis, similar local control for T3 mobile tongue with HDR in comparison to LDR with a majority receiving a combined treatment with EBRT.41 Leung et al. reported a 94.7% local control rate at 4 years for early stage oral tongue cancer with HDR interstitial brachytherapy alone.37

Figure 3.4 A remote high dose rate afterloader system (Nucletron Microselectron II, Nucletron Corp, Veenendal, NL). The remote afterloading unit that houses the 192Ir.

Figure 3.5 The computer console with printer that controls the unit. A proprietary treatment planning software package is loaded onto the computer.

Pulse Dose Rate

Pulse dose rate (PDR) brachytherapy is another approach, which combines the advantages of a remote afterloading technique with the radiobiologic benefits of LDR brachytherapy.42,43 Patients would receive a more frequent series of radiation fractions or “pulses” for duration of approximately 10 to 20 minutes in shorter interfraction interval of an hour over several days. Typically, a reduced activity source resulting in a medium dose rate of approximately 0.5 Gy per hour is used in a computer-controlled remote afterloading system analogous to the HDR system. However, the optimal dose rate and interval are still to be determined. During the procedure, the patients would be receiving treatment mimicking a continuous LDR treatment. However, the patient would not be restricted to the typical radiation precautionary restraints between treatments that minimize overall radiation exposure to personnel, allowing unrestricted access by the medical personnel and patient' visitors, especially with respect to the periods of loading and unloading of the source. In addition, with computer-generated treatment planning, further optimization may be possible without the restrictions of the available LDR source strengths. Many studies have been reported regarding the efficacy and the feasibility of PDR brachytherapy.44,45,46 Brenner et al. calculated equivalent radiobiologic effects for PDR (.5 Gy per hour given in a 10-minute pulse), and LDR (.5 Gy per hour given continuously).47 Further reports from calculations regarding differences in cell repair help support the approach of PDR.48,49,50

Multidisciplinary Team Approach

To perform a successful brachytherapy implant, a radiation oncologist needs the coordinated support of an experienced and well-informed team of a anesthesiologist, head and neck surgeons, plastic surgeons, a dental surgeon, and physicists. Coordination and placement of the surgical incision, grafts, drain and tracheostomy and wound closure techniques need to be meticulously planned and discussed before surgical procedure to optimize the implant geometry and reduce the risk of wound complications. In patients with temporary implants, it should be ensured that surgical drains and wound dressings are appropriately placed to avoid any hindrance to the source loading and unloading procedures. In addition, coordination of the wound closure procedure will minimize any potential tension, damage, and distortion of the implanted catheters and its geometry.

In the postoperative period, a well-trained nursing staff is also critical for care and use of this service is recommended. This allows potential avoidance of wound complications from the radiation that allows sufficient fibroblast to proliferate, as has been observed with brachytherapy treatments in extremity sarcomas.51

Following completion of the brachytherapy, removal of the catheters should be done with the coordination of the head and neck surgical team. Before the removal of the catheters, patients must have intravenous access. Suction, dressing materials, and adequate analgesics are also needed. A possible complication that may occur during the removal of the implanted catheters is arterial hemorrhage, which can be effectively controlled with bidigital compression. A review of the procedure, including a discussion of possible bleeding, should be clearly discussed with the patient to ensure proper cooperation and safety.

During the postimplant period, a review of the expected radiation side effects, including potential mucositis, pain, and decreased nutritional and fluid intake, should be carefully given before discharge. Education about these expected reactions is an important part of the patient care as is ensuring availability of analgesics, mouthwashes, and alimentation.

Various Head and Neck Sites


Cancer of the nasopharynx is primarily treated with RT with concomitant chemotherapy for locoregionally advanced disease.52 The nasopharynx is surrounded by multiple critical structures such as the brainstem, pituitary, optic chiasm, temporal lobes, cochlea, and salivary glands. Treatment of the nasopharyngeal tumors can be particularly challenging, especially for those that are locally advanced or recurrent. Tumor recurrences pose a greater challenge especially because the surrounding critical structures have received upper safe limits of radiation exposure. With the advent of 3D conformal RT, intensity modulated radiation therapy (IMRT), and stereotactic radiosurgery, the ability to treat with highly conformal RT is available. However, well-implanted brachytherapy can provide the most conformal treatment approach because of its steep dose falloff with distances and dose optimization potential. Therefore, the primary role of brachytherapy in the nasopharynx is in the management of recurrent disease or as a boost to EBRT in early stage cases.


Various technical approaches are available depending upon the location and extent of disease. The brachytherapy procedure can consist of either a permanent implant or temporary implants with the use of a choice of different isotopes including 125I, 137Cs, or 192Ir. When the entire nasopharyngeal mucosa requires irradiation, temporary intracavitary technique is optimal.53 This is ideal if the lesion is superficial and should not be used for more extensive lesions.54 If the lesion is discrete and localized, a permanent implant may be more successful with 125I sources.55,56,57 However, depending upon the site of disease within the nasopharynx, access for interstitial implantation may be difficult, especially for the superior or high posterior wall through the nasal or oral cavity. Permanent implants can be done through a transoral,58, a transnasal,59 or a transpalatal approach.60

If the lesion is located in the superior or high posterior wall of the nasopharynx, a transpalatal flap approach is used.61 A U-shaped incision is created along the hard palate up to the level of the greater palatine neurovascular bundles bilaterally with the creation of a posteriorly based flap, allowing for direct visualization of the superior aspects of the nasopharynx. The greater palatine vessels are preserved with this procedure. A Mick applicator is then used for direct implantation of the tumor. Upon completion of the implant, a previously custom-made prosthesis would be used to support the reapproximated soft palate for approximately 1 week to allow for adequate healing.

For lesions in the mid and low posterior wall of the nasopharynx, implantation access is through a transoral approach or through the nasal cavity without palatal fenestration. Harrison et al.58 describe a transoral approach with local control of the reported implanted patients. After the patient undergoes an orotracheal anesthesia, the soft palate is retracted to allow for visualization of the lesion using a dental mirror or a scope and implantation with 125I seeds with a Mick applicator through the oropharynx (see Figs. 3.6 and 3.7 for clinical examples). A transnasal approach also employs an orotracheal anesthesia and soft palate retraction. Using a Mick applicator, permanent seeds would then be implanted under visualization using a telescope in the oropharynx.59

Lesions in the lateral or anterior nasopharynx may be more ideally approached using temporary implants because of the anatomic composition and the tendency of the disease for lateral extension into the lateral retropharyngeal space. Harrison et al. describe a technique using a specialized applicator with flexible plastic tubes being placed curving toward the side of the nasopharynx.62 After treatment planning has been performed using dummy sources, a hole is drilled at a specific angle allowing for the placement of two angled 192Ir ribbons.

For intracavitary temporary implants, there are multiple applicators that are available. Basically, these involve the use of catheters or tubes that are placed into the nasopharynx. An inflatable balloon or cuffed tip applicator tubes can also be used to help secure the positioning and provide optimal distance from source to the mucosa for better depth dose distribution. These tubes can then be afterloaded with various radioactive sources such as 192Ir or 137Cs. After the placement of the temporary implant applicator, a computer treatment planning system would generate the radiation dosimetry for the given radioisotope. The delivery would include a dose distribution that covers the entire surface of the nasopharynx.

The planned radiation dose can vary depending upon the patient's prior radiation treatment and technique employed. In general, patients with recurrent disease receive 4,500 to 5,000 cGy with EBRT followed by brachytherapy boost to doses of 1,500 to 2,000 cGy.

Figure 3.6 A transpalatal flap approach for nasopharyngeal brachytherapy. After the U-shaped incision of the palate with preservation of the greater palatine vessels bilaterally. The sutures on the palate flap help provide the retraction for direct visualization of the nasopharynx. The tongue is retracted with a Dingman mouth gag. A trocar would then be inserted for permanent implantation into the nasopharyngeal tumor. (Courtesy of Louis B. Harrison, M.D.).

Figure 3.7 A plain film x-ray of an 125I seed implant of a nasopharyngeal tumor.


Several institutional series have reported sustained local control rates of 20% to 64% for recurrent disease, depending upon the extent of disease and dose administered.63,64,65,66 Fu et al. treated patients with a combination of limited external radiation and brachytherapy, obtaining a 5-year survival rate of 41%.58 Choy et al. reported the results of 43 patients treated with interstitial brachytherapy using gold seeds, obtaining a 5-year local control of 44% to 81% with a 5-year overall survival of 25% to 65%.68 Wang reported the results of reirradiation for recurrent nasopharyngeal carcinoma.67 He showed the importance of brachytherapy as part of the reirradiation treatment. With this approach, approximately half of the patients with relatively small recurrences were 5-year survivors.

Brachytherapy has also been given as a radiation boost for primary nasopharyngeal tumors or for persistent localized disease. Syed et al. reported on 15 patients with primary nasopharyngeal cancer with over 50% with stage IV disease who were treated with external radiation and intracavitary boost.63 The 5- and 10-year overall survival rates were 61% for both and the local control rates at 5 and 10 years were 93% and 77%, respectively. Wang also reported a markedly improved 5-year local control rate of 93% for those who received a course of external beam radiation of 64 Gy followed by a 7- to 10-Gy intracavitary boost.59


Cancer of the lip is the most common malignancy of the oral cavity. Fortunately, it usually presents as early stage lesions.69 These can be effectively treated with either surgery or RT alone. Surgical excision is recommended for small lesions that can be closed primarily without a cosmetic or functional deficit. However, excisions of many lip cancers, especially with involvement of the commissure, can result in significant cosmetic and functional sequelae. Therefore, RT provides an excellent therapeutic option in comparison to surgery, resulting in minimal cosmetic and functional disability.


For early stage lesions, radiation treatments can consist of interstitial brachytherapy either alone or with EBRT. Lip implants are typically done under local anesthesia. After the planned implant region has been anesthetized, small catheters are placed in parallel in a single plane with approximately 1 cm spacing (see Fig. 3.8 for a clinical example). Localization films are taken and computer treatment planning performed. The catheters are typically loaded with 192Ir or 125I sources delivering the desired radiation dose over several days. During the radiation treatment, the patient wears a dental lead-shielded prosthesis, providing radiation protection to the neighboring mucosa and mandible. In current practice, patients typically receive a total dose of 4,500 to 6,000 cGy over 6 days for interstitial brachytherapy alone for most early staged lesions. Patients with T3 tumors can be treated to slightly higher doses. If EBRT is utilized, the lip lesion would receive approximately 5,000 to 5,400 cGy followed by an interstitial implant of 2,000 to 3,000 cGy over 2 to 3 days.

Jorgensen et al. reported a large series of cases of lip cancer, consisting mostly of squamous cell carcinoma (SCC).61 There were 443 patients with T1 N0 disease, 337 cases with T2 N0 lesions, and 75 cases with T3 N0 lesions. The author reported a local control rate of 93%, 87%, and 75% for T1, T2, and T3 lesions, respectively in 766 patients treated with interstitial brachytherapy alone delivering a total dose of 2,500 to 5,600 cGy. The European Group of Brachytherapy reported their results of over 1,800 cases of lip cancer that were treated with a radioactive implant. The local control was 98.4%, 96.6%, and 89.9% for T1, T2, and T3 lesions, respectively.

Oral Tongue

Early stage oral tongue cancer can be treated with either surgery or RT with comparable rates of local control. Brachytherapy can offer optimal organ and function preservation either as primary therapy or as adjuvant after function sparing surgery. RT is preferably delivered with interstitial brachytherapy either alone or with EBRT. Brachytherapy alone can be used to treat most T1 or T2 lesions. For larger lesions, utilization of both external beam radiation and brachytherapy is preferred.

Figure 3.8 A patient with a small squamous cell carcinoma of the lower lip approaching to commissure, with a single plane low dose rate implant using angiocatheters loaded with 192Ir.



There are various technical approaches to an interstitial oral tongue implant. Among the available techniques, the loop technique, as previously described, is preferred. During this operative procedure, the patient would have already undergone any planned neck dissections. Unlike in a base of tongue implant, a tracheostomy is not always required for airway protection. If the tumor approaches the base of tongue, some may need a temporary tracheostomy to protect the airway from tongue swelling and bleeding. Before catheter placement, delineation of the planned number of catheters and entry/exit points as well as identification of various normal structures, including the facial artery, carotid artery, and the hyoid, is important. Basically, a curved metal trocar is introduced into the submental region and aimed toward the intended exit site in the tongue directed by the index finger of the physician's other hand. Afterloading catheters are threaded through the trocar and then looped over the tongue mucosa and out through the similarly introduced adjacent trocar (Fig. 3.6 for a clinical example). The placement of any catheter adjacent to the mandible should be avoided because of the risk of osteoradionecrosis. The spacing between the loops and the adjacent limbs is approximately 1 cm. Upon completion of the implant, orthogonal verification films are taken with loaded dummy sources. The exposed catheter limbs can then be tied together within a penrose drain. The catheters are loaded with 192Ir ribbons once patients are comfortable with self-care of a peg tube and/or tracheostomy care. Patients should wear the custom-designed radiation protective dental prosthesis for added protection to the mandible.

For larger T2 and T3 lesions, a combination of EBRT and interstitial brachytherapy is preferred. For N0 patients, a dose of approximately 5,000 cGy in 5 weeks is given to the primary site and neck. After 2 to 3 weeks, an interstitial implant is performed to deliver a boost dose of 2,000 to 3,000 cGy. For patients with positive neck disease, 5,000 cGy is delivered to the primary lesion and upper neck with a boost of 6,000 cGy gross nodal disease followed several weeks later with a planned neck dissection and the interstitial tongue implant during the same operative procedure.


There is a significant body of literature supporting the role of interstitial brachytherapy in the management of oral tongue cancer. One of the largest reported studies, with over 600 patients, in the treatment of T1–3 squamous cell of the oral tongue cancer is by Decroix and Ghossein from the Curie Institute in Paris.70 Treatments included EBRT, interstitial brachytherapy, and surgery, either alone or as a combination therapy. Most patients were treated with brachytherapy alone, especially those with T1 and T2 disease, with a radiation dose of 6,000 to 7,000 cGy over 6 to 9 days. Larger T2 and T3 tumors were treated with a combination of EBRT (5,000 to 5,500 cGy) and interstitial brachytherapy (2,000 to 3,000 cGy). The reported local controls rates were 86%, 80%, and 68% for T1, T2, and T3 lesions, respectively. Mazeron et al. reported on 166 patients with early staged T1–2 lesions treated with interstitial brachytherapy.71 One hundred and fifty-five node negative patients had a 5-year local control rate of 87%. This compares favorably with a surgical series from Memorial Sloan-Kettering Cancer Center in New York with local control rates of 85%, 77%, and 50% for T1, T2, and T3 lesions, respectively.72 Additional reports suggest better local control when a greater proportion of dose is administered with an implant.

Adjuvant brachytherapy may be considered in radically resected tumors with close or positive margins, especially if further surgical resection would lead to significant functional disability. Ange et al. reported the outcome of 23 patients with oral tongue and floor of mouth (FOM) malignancies that underwent an excisional biopsy. These patients were then treated with interstitial brachytherapy with doses of 5,500 to 6,000 cGy, obtaining 100% local control.73Mendenhall et al. reported the results of 16 patients consisting of 9 oral tongue and 7 FOM cancers who underwent an excisional biopsy.74 The margin status was positive in six patients, questionable in seven, unknown in two and negative in the remaining one patient. Half of the patients were treated with interstitial brachytherapy, either alone or combined with EBRT. Excluding one patient who died of intercurrent disease, in all seven patients with FOM cancer and seven of the eight remaining patients with oral tongue cancer, local control was achieved. Hu and Harrison also reported the results of 13 patients with T1–2 SCC of the oral tongue and FOM after undergoing surgical resection with close or positive margins.75 All patients had pathologic N0 neck dissections except for one patient with N1 disease. These patients were treated with interstitial brachytherapy alone with LDR 192Ir with a median dose of 5,000 cGy. There were no local failures. Two patients developed a recurrence in the neck with one of the patients treated with additional surgery and EBRT. Overall survival was 92% with no distant metastatic disease.

The two main complications are soft tissue necrosis and osteonecrosis. Typically, soft tissue necrosis is a self-limiting process, healing with time. However, osteonecrosis can be severe and may require mandibular resection. Mazeron et al. performed a retrospective analysis on the prognostic factors for local control and brachytherapy complications in the treatment of T2 oral tongue cancers. The authors then divided the T2 lesions on the basis of tumor size into T2a (2.1 to 3.0 cm) and T2b (3.1 to 4.0 cm). By increasing the radiation dose, patients with T2a lesions had an increase in local control from 73% to 92% for a dose level from 5,500 to 6,000 cGy to 6,500 to 7,500 cGy. However, the risk of soft tissue necrosis also increased from 16% to 33%. The authors recommended a dose of 6,500 cGy to achieve good median between excellent local control and a more acceptable soft tissue necrosis level.

Floor of Mouth

As with oral tongue carcinoma, early staged FOM cancers can be successfully treated with either RT or surgery. Currently, surgical resection is often preferred because high local control rates with excellent functional outcome can be attained. In addition, the proximity of the mandible to the FOM increases the potential serious complication risks of osteonecrosis. Brachytherapy can still be appropriately implemented in the management depending upon the clinic scenario, including surgical unfeasibility or medical contraindication.


FOM implants are essentially similar to the approach for oral tongue implants. A looping technique is preferred. However, the proximity of FOM to the mandible can pose a significant risk for osteoradionecrosis, requiring great care and attention during implant placement.28 Depending upon the extent of disease, this may be impossible to avoid, resulting in significant risk of bone exposure or osteonecrosis. A lead mandibular shield should be placed to minimize the risk. However, caution must be taken regarding the size and placement of the shield to avoid obstruction of the implant and unintended protection of the tumor.


When RT is employed in the management of FOM cancers, there have been numerous reports supporting the use of brachytherapy as part or all of the radiation treatment. Chu and Fletcher compared the outcomes for patients with FOM cancer treated using EBRT alone, brachytherapy alone, or a combination of EBRT and brachytherapy. 76 There was a significant improvement with the use of brachytherapy either with EBRT or alone, resulting in local controls of 98%, 93%, and 86% for T1, T2, and T3 lesions, respectively. Pernot et al. reported their experience with 207 patients with SCC of FOM treated with definitive RT consisting of EBRT and brachytherapy (105 patients) or brachytherapy alone (102 patients). The 5-year local control was 97%, 72%, and 51% for T1, T2, and T3, respectively.77 In addition, the authors found that brachytherapy alone has a better prognosis for T1 T2 N0 patients, particularly with T 2 N0 with improved local control and specific survival rates.28,77 There was a reported 6% severe complication rate with one fatality. Mazeron et al. reported on their experience with FOM cancers treated with definitive brachytherapy where they obtained a primary local control of 93.5% and 74% for T1 N0 and T2 N0 patients, respectively.78 Tumor size and gingival extension were found to negatively affect local control. Matsumoto et al. reported similar results for those undergoing brachytherapy mostly with 198Au grains.79 The local control was 89%, 76%, and 56% for T1, T2a (≤ 3 cm), and T2b (>3 cm), respectively. In addition, the local control was 82% for patients with T1–2 N0 disease without gingival extension and 55% for those with gingival involvement. Marsiglia et al. reported the experience of The Institut Gustave-Roussy with patients with FOM cancer who underwent definitive brachytherapy with a long follow-up of 9 to 19 years.80 The local control rates were 93% and 88%, for T1 and T2 lesions, respectively. There was an incidence rate of 18% with bone necrosis, which was mostly treated with conservative medical measures. Patients with poor dental status and lack of dental shield were much more likely to have bone complications.

The risk of osteoradionecrosis is clearly a major disadvantage of brachytherapy for the treatment of FOM lesions. Morrish et al. found that osteoradionecrosis is related to the dose and postradiation extractions.81 Doses of >7,500 cGy resulted in 50% or higher rates of osteoradionecrosis. Beumer et al. reviewed 83 cases of osteoradionecrosis with 78 involving the mandible.82 The authors found that the most common precipitating factors were postradiation extractions, periodontal disease, and preradiation extractions. In addition, 44% of those cases who received >7,000 cGy needed to undergo mandibular resection. Proper attention to dental care shielding, patient selection, brachytherapy technique and dose may help minimize this complication.

Buccal Mucosa

Cancer in the buccal mucosa is rare, especially in the western world. They are more frequently seen in Southeast Asian countries, particularly because of the common use of chewing tobacco- and areca nut–containing products, which are associated with oral cavity cancer.83 This can lead to oral submucous fibrosis, which is a precancerous lesion in the mouth and associated with oral cancer.84 In this setting, interstitial brachytherapy alone may be an option. For advanced lesions, surgery or a combination of EBRT and brachytherapy are possible treatment options.

There are several technical approaches to the implantation. Lapeyre et al. described two techniques in the treatment of buccal mucosa.85 Patients were treated with either a parallel wire technique or a loop technique. The latter method consists of a loop or radioactive wires to encircle the tumor posteriorly, which is similar to the method for oral tongue or FOM lesions. The brachytherapy procedure can be performed under general or local anesthesia. Typically, a single parallel plane implant is possible for thin lesions <1 cm in thickness. Otherwise, a multiplane implant may be necessary. The number of catheters and insertion and exit sites are determined to ensure proper coverage of the tumor with the catheters running in a parallel fashion. Angiocatheters or metal trocars are inserted through the skin near the labial commissure, transversing through the tumor to exit percutaneously. The catheters can be secured in place by crimping a metal button at the entrance and exits sites. If the lesion is situated posteriorly, the looping technique can then be utilized to ensure adequate marginal coverage of the lesion. Care must be taken to maintain a minimum distance of 0.5 cm to the nearest catheter to the mandible. 192Ir ribbons can then be afterloaded into the catheters. Customized mandibular lead-lined shields should be used along the buccal-alveolar sulcus for providing radiation protection to the surrounding structures including the mandible.

Lapeyre et al. compared the two techniques in 36 T1–3 patients with a median dose of 6,550 cGy.85 The authors reported that 6 out of 14 patients had local failure with the parallel wire technique compared with 1 out of 22 patients with loop technique. The 5-year actuarial local control was 91% and 58% for the loop and parallel wire techniques, respectively. There was a 17% incidence of complications observed in 42 patients (in conjunction with patients not in the original comparison) including those occurring after salvage surgery or local recurrence. These complications generally consisted of soft tissue necrosis. One of the largest reviews of buccal mucosa cancers is by the European Group of Curietherapy.86 Seven hundred and forty-eight patients who were treated with brachytherapy alone (226 patients), or brachytherapy with EBRT (80 patients), or EBRT alone (273 patients) were followed up for a minimum of 3 years. Brachytherapy alone was carried out if the lesion was <5 cm in size. Local control rates were 81% for brachytherapy alone, 65% for the combined treatment, and 66% for external radiation alone. Another large series was published by Nair et al.87 In that series of 234 patients with T1, T2, and T3 buccal mucosa cancer, interstitial implant was undertaken to deliver a dose of 65 Gy over a period of 6 days. Stage-specific disease-free survival was 75%, 65%, and 46% for T1, T2, and T3 tumors. Large tumors also require radiation treatment to the neck.

Base of Tongue

SCCs of the base of tongue usually present in a locoregionally advanced stage because of the high propensity of lymph node involvement, their relatively occult location, and insidious growth pattern in an area devoid of pain fibers.88 The management of cancer of the base of tongue has evolved significantly over the past decade. Traditionally, major resections were the recommended treatment course for advanced base of tongue cancer followed likely by postoperative RT. Because the tongue has a significant role in the routine, daily functions, surgical resection can produce severe functional handicaps in speech and eating. Presently, most patients have an opportunity to be treated using an organ preservation approach.8108990919293

Multidisciplinary integration of EBRT with brachytherapy, concurrent chemotherapy, and planned neck dissections offer the best chance for optimal outcomes.


Brachytherapy is an attractive method for providing conformal dose escalation to the tumor typically after EBRT. A loop technique would be performed similar to that for the oral tongue. The implant is usually done after an interval of 2 to 3 weeks from the EBRT. A longer period may be necessary after a course of concomitant chemoradiation therapy to allow for adequate healing following the treatment. The technical approach is similar to the implant for the oral tongue using a loop technique as previously described (see Figs. 3.9, 3.10 and 3.11).

Brachytherapy is typically used as a boost to the base of tongue after a course of reduced-dose conventional fractionated EBRT that treats the bilateral necks and primary site to a dose of 5,400 cGy. Gross nodal diseases are typically boosted to a total dose of 6,000 cGy (54 Gy to the tongue base, 54 to 60 Gy to the necks). A dose of 20 to 30 Gy is typically delivered as a low dose rate 192Ir implant, thereby increasing the cumulative dose to, most commonly, 74 to 81Gy. For T3 and T4 base of tongue tumors, higher initial EBRT doses are usually given followed by reduced dose implant (1,000 to 1,200 cGy).

Figure 3.9 A patient with squamous cell carcinoma of the oral tongue. Delineation of the target volume is made under anesthesia with a surgical marker and catheter entry sites.

Figure 3.10 Using a plastic tube looping technique, the entire tumor volume is implanted.


Figure 3.11 Localization films taken with dummy sources for dosimetric planning.


The role of brachytherapy has a long, proven history with excellent control rates for base of tongue cancers when combined with EBRT without concurrent chemotherapy. Local control of 80% to 90% for T1–3 disease is consistently reported and results of ≥67% to 100% for selected T4 disease have been reported as well (see Table 3.1). Harrison et al. have reported the long-term results of 68 patients mostly with stage III or IV base of tongue cancer treated between 1981 and 1995 with combined EBRT (54 Gy) plus 192Ir implant (20 to 30 Gy) combined with planned neck dissection for patients presenting with involved nodes.11 Nodal disease was clinically evident in 85% (58/68) and staged as N2 or greater in 50% (34/68). Thirteen percent (9/68) who would have required a total laryngectomy, if managed surgically, received induction chemotherapy. No patient received concurrent chemotherapy. At a median follow-up of 36 months, the 5- and 10-year actuarial rates of local control are 89%, distant metastases-free survival is 91%, disease-free survival is 80%, and overall survival is 86%. All T stages (T1 = 17 patients, T2 = 32 patients, T3 = 17 patients, T4 = 2 patients) were combined together as there were no differences in local control when analyzed by T stage (T1, 87%; T2, 93%; T3, 82%; and T4, 100% at 5 years). With planned dissection after a reduced dose of EBRT, regional control was 96% at 5 years. Complications after the implant and EBRT occurred in 19% including (i) soft tissue ulcer in 13% (9 patients), all of which healed; (ii) osteoradionecrosis in 3% (2 patients), requiring mandibulectomy, and (iii) brisk bleeding during catheter removal in 4% (3 patients), all of which were controlled at the bedside with tamponade and suction.

Many other authors have reported consistently high local control with EBRT and brachytherapy. Crook et al. reviewed the results of T1 and T2 patients treated mostly with external radiation and interstitial implant.94 Five-year local control rates were 85% and 71% for T1 and T2, respectively. Goffinet reported similar results in their series of patients, staged mostly III and IV, treated with combined EBRT and brachytherapy, revealing that a 71% remained disease free at a median follow-up of 32 months with 5-year actuarial survival of 70%.95 An update was published on the outcomes of 41 patients. The 5-year local control rates were 86%, 86%, 90%, and 70% for T1 to T4, respectively. The 5-year overall survival rates were 43% and 71% for stage I/II and stage III/IV, respectively.96 Horwitz et al. treated 20 patients with base of tongue cancer with a combination of external beam radiation and interstitial boost of 125I seeds.97 The 5-year actuarial local control rate and overall survival was 88% and 72%, respectively. Puthawala et al. reported their 10-year experience in the treatment of 70 patients with base of tongue cancer.98 The authors showed that the overall local control was 83% and the absolute 3-year disease-free survival for the entire group was 67%.

Table 3.1 External Beam Radiation Therapy with Interstitial Implant


Local Control (%)

Five-year Overall Survival (%)

Late Complications (%)






















Stage I/II = 43




Stage III/IV = 71





















aIncludes all patients.
bIncludes a 2-year actuarial survival for all patients.
Data from References8,9,10,11,33,96,98.

One of the few series in the literature that compares outcomes using different treatment modalities was reported by Housset.10 In this series, T1–2 patients were treated with EBRT alone, EBRT plus brachytherapy, or surgery plus postoperative RT. The groups were well balanced, except that there were more patients with purely exophytic lesions in the EBRT-alone group. Despite this potentially more favorable unbalance, the local failure rate was twice as high in that group (40% vs. 20%). This study suggests that EBRT plus implantation is superior to conventional EBRT and is oncologically equivalent to surgery plus postoperative RT. Brachytherapy combined with EBRT has shown consistent high local control rates likely because of the ability to achieve dose escalation, with an implant. Puthawala et al. also noted a dose response relation with higher local control associated with cumulative doses of at least 75 Gy.99 Analysis by and Goffinet et al.100 and Regueiro et al.101 also validate the concept that addition of a brachytherapy implant improves local control and preserves function in patients with early stage base of tongue cancer. Han et al. also reported retrospectively on 18 patients with T4 base of tongue cancer from 4/98 to 12/04 treated with definitive RT including brachytherapy boost.102 Seventeen patients received concomitant chemotherapy. With a median follow-up of 23 months, the crude local control rate was 83% (15/18), and the regional control was 100%. The 2-year Kaplan Meier actuarial estimates of local control (LC), regional control (RC), locoregional control (LRC), distant metastasis (DM), disease free-survival (DFS), and overall survival (OS) were 84%, 100%, 84%, 36%, 50%, and 100%, respectively. The one patient who did not receive chemotherapy failed locally.

Quality of Life

Harrison et al. reported on the quality of life issues and performance status in patients with base of tongue cancer treated with EBRT with brachytherapy boost versus primary surgery.100 A Performance Status Scale (PSS) for Head and Neck Cancer developed by List103 was one of the scales used for the assessment. This scale, scored from 0 to 100, evaluated the three basic functions of eating in public, understandability of speech, and normalcy of diet. For eating in public, patients with T1–2 tumors had a score of 85 versus 75 (p = 0.31), and T3–4 patients had a score of 82 versus 35 (p <0.001) for radiation versus surgery, respectively. For understandability of speech, T1–2 patients had scores of 92 versus 65 (p = 0.0021), and T3–4 patients had scores of 95 versus 35 (p <0.0001) for radiation versus surgery, respectively. For normalcy of diet, T1–2 patients had scores of 74 versus 50 (p = 0.047), and T3–4 patients had scores of 78 versus 32 (p = 0.0012) for radiation versus surgery, respectively. Various other scales were used including Memorial Symptom Assessment Scale (MSAS), the Functional Assessment of Cancer Therapy (FACT), and a sociodemographic and economic questionnaire, were reported.8 All patients treated with brachytherapy were highly functional in all three categories regardless of whether their tumors were early or advanced stage. FACT surveys revealed that 72% were able to maintain their full-time employment status while the majority could maintain their income and socioeconomic quality of life. The major quality of life issues in these patients include xerostomia and potential swallowing difficulty. Horwitz also found excellent performance status scores for eating in public, understandability of speech, and normalcy of diet for patients treated with EBRT and brachytherapy.93

Faucial Arch and Tonsil

SCC of the faucial arch and tonsil are relatively rare in the United States. Overall, squamous cell cancers arising in the anterior tonsillar pillars and soft palate have better prognosis when compared with tonsillar fossa lesions.104 Tumors limited to the posterior tonsillar pillar are rare. Early staged lesions can also be treated effectively with either RT or surgery. RT is generally preferred because of the excellent local control and functional outcome. Typically, EBRT is employed to treat the primary gross lesion and its nodal draining basins followed by a brachytherapy boost.


The general brachytherapy approach differs significantly depending upon the location of the lesion. The best described approach is the Pernot Technique.105 In this implant, a plastic tube technique is utilized.

The patient is placed in a seated position with the head in a vertical position. Identification of all the critical neighboring structures, which include the hyoid and thyroid cartilages, carotid and facial arteries, and the lateral position of the pillars, is performed. The patient is implanted under conscious sedation with local anesthesia to the skin, tonsillar pillars, and the soft palate. Soft palate lesions are implanted with two parallel catheters traveling in a left-to-right direction from the anterior cervical neck through the tonsillar pillar, transversing the entire course of the soft palate and exiting through the contralateral tonsillar pillar and neck. Starting with the left tonsillar pillar, a metal guide needle is inserted horizontally below the hyoid bone at the distance from the midline that matches the tonsillar pillar. After transversing approximately 2.5 cm horizontally, the needle is directed superiorly to the base of the posterior pillar. The other free hand is placed to help direct the needle and ensure that the pharyngeal wall is not punctured. At the base of the left posterior tonsillar pillar, the needle is redirected to the top of the tonsillar pillar along the posterior pillar, finishing with the needle tip piercing the adjacent mucosa. A nylon fishline is then introduced into the mouth through the guide needle and held in place. In a similar manner, another guide needle is percutaneously introduced above the hyoid bone and 1.5 cm from the prior entry point. This guide needle is then tracked up parallel to the other needle along the left anterior pillar, ensuring that it is at least 0.5 cm from the mandible. A nylon fishline is similarly placed followed by the removal of the guide needles. Then plastic tubes are introduced with the nylon fishline by clamping the inferior end to the plastic tube at least 10 cm from the end, and then pulled upward intraorally. Fluoroscopy can be done to check placement and parallel alignment. With the same technique, the contralateral tonsillar pillars are implanted with nylon fish line. With a specialized long thin curved needle, a track is made from the upper exit site of the guide needle along the inferior edge of the soft palate and out through the contralateral side of the uvula. Another nylon fishline is threaded through the needle and left in place. The needle is then reinserted through the same exit site and tracked along the inferior portion of the soft palate and out through the corresponding exit site of the previous guide needle. Another nylon fishline is then left in place. With the laid out nylon fishline, the plastic tube in the left posterior tonsillar fossa is placed along the soft palate and taken out through the contralateral posterior pillar. These steps are repeated for the anterior half, ensuring parallel alignment with 1.5 cm spacing. If the adjacent base of tongue is involved, additional loops are to be placed under general anesthesia. If the tonsillar fossa lesions are low lying, an ipsilateral looping can be performed between the two pillars with the Reverdin needle. Upon completion, the typical radiation planning would be performed.

If brachytherapy is planned, doses are generally 4,500 to 5,000 cGy with EBRT followed by a brachytherapy boost of 2,000 to 3,000 cGy. Regarding the time interval, Hoffstetter analyzed various treatment factors and reported that a break of >20 days and an overall treatment period beyond 7 weeks were prognostic for poorer local control and survival.97


Pernot et al. reported one of the largest studies on T1–3 SCCs of the velotonsillar region treated by either a combination of EBRT and brachytherapy (343 patients) or brachytherapy alone (18 patients) with 192Ir.106 The patient distribution with respect to cancer site was as follows: Tonsils, 128; soft palate, 134; posterior tonsillar pillar, 9; anterior tonsillar pillar, 63; and glossotonsillar sulcus, 27. The 5- and 10-year local control rates were 80% and 74%, and the overall survival rates were 53% and 27%, respectively. The 5-year local control was 87% and 67% for T1–2 and T3, respectively. Also the local control for N0 was 80%, while was 55% for N +. Mazeron et al. reviewed the outcome of 165 T1–2 patients with faucial arch squamous cell cancer who were treated with either EBRT or brachytherapy, or a combination of both.107 In this study, 5-year local control was 58%, 100%, and 91% with 5-year overall survival being 21%, 50.5%, and 60% respectively. Because there was an improved local control and survival with brachytherapy, the authors recommend that T1–2 tumors of faucial arch be treated with EBRT of 4,500 cGy followed by a brachytherapy boost of 3,000 cGy. Various published reports on brachytherapy showed that it was typically administered as a boost (2,000 to 3,000 cGy) following EBRT (4,500 to 5,000 cGy) because of the risk of lymph node metastases, especially for the posterior tonsillar pillar lesions requiring treatment of the retropharyngeal lymph nodes.106,107,107,108,109,110 Typically, with combined EBRT and brachytherapy, the local control rates are 85% or greater for T1–2 lesions and 65% to 70% for selected T3 lesions. Amornmarn et al. reported that a combined approach for tonsillar cancers resulted in improved local control and overall survival with good function and quality of life.112 Le Scodan et al. treated 44 patients with T1–2 velotonsillar cancers with interstitial brachytherapy alone after limited resection including 8 patients with prior history of EBRT. With a median follow-up of 75 months, the author found only one local failure and four nodal failures, occurring in undissected necks.

Levendag et al. retrospectively analyzed the results of 38 patients with SCCs of the tonsil and soft palate treated using PDR or fractionated HDR brachytherapy either alone or combined with external irradiation.30 These results were compared with those obtained in 72 patients who were treated with external beam radiation alone. Their analysis indicated that there was no difference in the local relapse-free survival or overall survival between the two groups, at 3 years of follow-up.

Recurrent Squamous Cell Carcinoma in the Head and Neck

Recurrent cancer in a previously irradiated field poses a difficult challenge as patients would have often received extensive multidisciplinary treatment and present with biologically aggressive locoregional disease and are at high risk for distant metastases. In addition, retreatment is associated with high rates of severe complications. Balancing these risks with the limited chance for salvage requires careful patient selection and meticulous multidisciplinary evaluation. Before initiating any therapy, patients should undergo a complete staging workup to help determine the overall treatment strategy and the “curability” of the disease, in addition to assessing the patient's overall medical condition and performance status.


Treatment options vary depending upon the site of recurrence. Typically, the overall strategy requires evaluation for resectability and the ruling out of distant metastases. If resectable, salvage surgery alone may not be adequate and radiation may be required. Reirradiation with EBRT and/or chemotherapy is possible but with increased risk of severe toxicities such as pain, wound breakdown, bleeding, infection, fistula formation, bleeding, and necrosis.98,112,113,114,115,116Surgery is generally recommended even if sacrifice of adjacent structures such as the eye or larynx is required for oncologic clearance. Given its high conformality characteristics, brachytherapy provides an attractive treatment option either as adjuvant therapy or as definitive therapy. Reconstruction with nonirradiated soft tissue flap at the time of brachytherapy implant can reduce the risk of wound complications.118,119


The technical approach can vary depending upon the extent of disease, location of tumor, presence of critical normal structures, surgical accessibility, and prior RT. A temporary or a permanent implant can be performed. Permanent implants typically using low activity 125I seeds are preferred when there is residual gross disease or involvement of a vital structure like the carotid artery in the neck, which may not be resectable. Interstitial implants can be also performed with a variety of approaches. With the use of a Mick applicator, direct volume implants can be performed into residual gross tumor. The Anderson nomogram can estimate the number of seeds on the basis of seed activity and the average dimension of the volume implant.120 Delineation of the volume of disease is crucial to ensure a successful implant. The seeds are usually spaced approximately 1 cm apart. Upon completion, dosimetric calculations are performed using computed tomography (CT) scan or orthogonal localization films. Suture seeds can also be used for a single plane implant. The suture seeds are directly sewn into the tumor bed, typically 1 cm apart. This may be ideal in cases following total gross resection where there is high risk of residual microscopic disease. If the disease is resected adjacent to the carotid artery, a permanent implant can be facilitated by the use of a Dexon mesh. The suture seeds are sewn directly into the mesh in a parallel fashion. The mesh is then implanted over the entire tumor bed. Typically, the dose is 144 Gy to the tumor volume if possible. With either method, a nonirradiated soft tissue flap should be used for reconstruction of the neck to minimize any potential reirradiation complication such as a carotid blowout.

In addition to permanent implants, temporary implants can be similarly performed. The approach would be customized depending upon the location of disease. Various techniques are possible. Using an approach similar to the plastic tube technique, afterloading catheters are placed over the tumor bed. After maximal total gross resection, the surgical tumor bed is identified. Surgical clips demarcate the planned treatment region for future reference. The orientation of the implant is such that the catheters are spaced far enough from the suture line to minimize wound-healing complications and are positioned so that there is minimal physical displacement after reconstruction and during patient movement. The planned skin entry sites are demarcated so as to be approximately 1 cm apart to cover the tumor bed with adequate margin, in addition to being at least 1 cm away from the planned wound closure site. A sealed end technique is often preferred. A metal trocar is percutaneously introduced through the skin entry points along the direction of the planned implant. A nylon afterloading catheter is threaded through the trocar and then sutured in placed after removal of the trocar over the surgical bed using an absorbable suture. The proximal end of the catheter is placed beyond the surgical bed to ensure proper coverage with margin. This step is repeated, resulting in parallel alignment of the catheters covering the tumor bed. If the area includes the carotid artery, a mesh can be used to place the catheter over the artery thereby avoiding puncturing the vessel. This procedure is similar to that described for suture seeds. The catheters are secured with a metal button, which is crimped and sewn to the adjacent skin. After completion of the implant, the exposed end of the catheters can be cut with ample remaining length and secured with a penrose drain. Fluoroscopic verification is done to check catheter placement with dummy sources. The usual radiation planning is performed. The patient is loaded after 5 or more days to allow for adequate healing. A clinical example of this is portrayed in Figures 3.12A and B.

Neck Results

Goffinet et al. described a permanent neck implant using 125I seeds impregnated in vicryl suture material.121 In 53 unirradiated patients treated with this technique, effective local control in the head and neck region was obtained in 71%. In 38 patients who had been irradiated previously, local control was 59% with 38% of the patients exhibiting no recurrence in any head and neck site. Choo et al. reported on 20 patients with recurrent or persistent neck metastases with 192Ir implants.122 In addition to the implant, the treatment consisted of salvage surgery for nine patients, combined EBRT for three patients, and brachytherapy alone for eight patients. They reported that in 15 patients, immediate local control was 100%. At 27 months' follow-up, 25% were alive. Cornes et al. analyzed the outcome for 39 patients with inoperable neck nodes who underwent maximal surgical resection and reradiation with implantation of 192Ir seeds with or without reconstruction flap.123 In the 13 patients without the reconstruction, the local control rate at 1 year was 68%. However, 46% also experienced severe radiation-induced fibrosis and neck contracture. In the remaining 26 patients with a reconstruction flap, local control at 1 year was 63%, with significant morbidity in 12%. Bollet reported on 84 patients with isolated cervical metastasis treated mostly with brachytherapy alone (72 patients with mean dose of 5,650 cGy) or a combination of EBRT and brachytherapy (12 patients with mean dose of 38 Gy with brachytherapy and 41 Gy with EBRT) without surgery.124 The lymph node control was 22% and 0% at 2 and 5 years, respectively. If the total dose was ≥60 Gy, the control improved to 56%. Significant toxicity occurred in 35% with 7% being fatal. The authors concluded that salvage surgery should always be performed when possible.

Figure 3.12 Two different cases of isolated solitary nodal recurrence after irradiation. Two patients undergoing temporary interstitial brachytherapy implant for a large nodal recurrence and prior radiation therapy.

Other Head and Neck Sites

Brachytherapy alone can be utilitized for certain select patients. Puthawala published data on a large series of 220 patients with recurrent or new primary tumor in head and neck with prior RT that were treated with interstitial brachytherapy with or without chemotherapy or interstitial hyperthemia.125 The median minimum tumor dose was 5,300 cGy. The authors reported local tumor control of 77%, 69%, 51%, and 41%, respectively, at 6 months, 2, 5, and 10 years. The disease-free survival at 2, 5, and 10 years was 60%, 33%, and 22%, respectively. Moderate to severe complications were seen in 27%. Peiffert et al. reported the results of 73 patients with velotonsillar carcinoma in a previously irradiated field treated with brachytherapy with a mean dose of 6,000 cGy.126The 5-year actuarial local control rates for T1 N0 and T2 N0 lesions were 80% and 67%, respectively. Grade 2 self-resolving complications mostly of soft tissue necrosis were observed in 10 patients (13%) who received doses >60 Gy and there was no grade 3–4 toxicity. The incidence of these complications was higher when compared with the same institution's series of tonsillar implants in unirradiated tissues. The 5-year actuarial disease-specific survival and overall survival were 64% and 30%, respectively. The authors also observed that 42% of deaths were secondary to malignancies with all but two who continued to use alcohol and tobacco. Mazeron et al. reported an actuarial 5-year local control of 69% in previously irradiated patients with oropharyngeal cancer treated with 192Ir brachytherapy.127 Patients with faucial arch and posterior pharyngeal arch had a 100% local control. However, glossotonsillar sulcus and base of tongue tumors had worse local control of 69%. Tumor size (>2 cm) also adversely influenced the local control rate, with larger lesions mostly in the base of tongue. Only 7 of 69 patients (10%) developed nodal relapses. The main complication was soft tissue necrosis (27%) and was self-resolving in 13 of 14 patients. The incidence of this complication appeared to increase among cases in which a large lesion was treated with an implant. Stevens et al. reported on reirradiation for patients with new second primaries or recurrent disease that was treated with EBRT, brachytherapy, or both, noting favorable local control rates with a reirradiation dose 6,000 cGy for second primary head and neck SCC, a treatment interval >1 year for recurrent lesions, and the use of an implant in addition to EBRT.128 Park et al. analyzed 35 patients with advanced recurrence of SCC of the head and neck treated with surgery with a 125I seed implant because of positive or close margins on frozen sections.129 The authors reported a determinate 5-year disease-free survival of 41% and 29% with no evidence of disease. However, there was a 36% rate of significant complications.

HDR brachytherapy has also been increasingly utilitized even in recurrent diseases. Leung et al. reported the results of locally recurrent nasopharyngeal cancer treated with either EBRT alone (41 patients), HDR intracavitary brachytherapy (8 patients), or a combination approach (42 patients).130 The median dose was 50 Gy with EBRT and 14.8 Gy over 3 weekly sessions for the combined group, 24 to 45 Gy in 3 to 10 fractions for HDR alone, and median of 57.3 Gy (equivalent dose). The authors reported a 5-year actuarial overall survival rate, disease-specific survival rate, and local failure–free survival rate of 30%, 33%, and 38%, respectively. However, there were significant amounts of complications, with 57% of the patients having at least one major complication. Hepel et al. reported the outcomes in 30 patients with recurrent previously irradiated head and neck cancer.131 Patients were treated with HDR interstitial brachytherapy with a mean dose of 34 Gy in twice-a-day fractions of 300 to 400 cGy per fraction. With a minimum follow-up of 12 months, the local tumor control rate was 69% with a 2-year overall survival of 37%. Grade 3–4 complications rate was 16%. Further studies are needed to evaluate the role of HDR, especially in the setting of recurrence.

Intraoperative Radiation Therapy

Intraoperative radiation therapy (IORT) is another attractive approach to deliver temporary HDR brachytherapy. This technique refers to the application of a single high dose of RT during an operative procedure, usually after maximal resection of gross tumor.132 Direct visualization of the tumor bed at risk is possible while neighboring normal tissues can be displaced or shielded, thereby optimizing dose delivery. Another added benefit would be the opportunity to treat when the tumor burden is at its lowest and the adverse effects of hypoxia may be less influential in comparison to the postoperative period.

The earliest reports of IORT can be dated back to beginning of the twentieth century. In 1905, in Spain, Comas and Prio delivered fractionated intra-abdominal IORT after total abdominal hysterectomy, pelvic lymph node dissection and partial cystectomy for locally advanced cervical cancer.133,134 In 1907, Beck reported the treatment of an advanced pyloric cancer.135 The ability to perform IORT evolved as the available technology developed. IORT was first introduced in the United States by Henschke and Goldson in 1975, who used a linear accelerator.136 Various applications have been available to deliver radiation in the form of photons and electrons, especially the latter, with the advent of modern linear accelerators. IORT is most commonly delivered using electrons.54However, the use of a linear accelerator in a dedicated shielded operating room is costly, in addition to the logistic difficulty in some scenarios of intraoperative transportation to the radiation oncology department.

Another intraoperative delivery technique is through the utilization of an HDR remote afterloader with 192Ir sources, which can provide an advantage with regard to expense, mobility, and the absence of unwieldy applicators. A shielded room with radiation security monitoring is still required for treatment, in addition to an adjacent “clean” room for observation of the patient during the treatment. An intraoperative applicator for the HDR IORT can virtually conform to surfaces with any shape that allows optimal geometry and dosimetry. A Harrison-Anderson-Mick (HAM) applicator is a specialized 0.8-cm thick pad of transparent flexible material with embedded source guides running through the center, which can be attached to the remote HDR afterloading system. The number of channels can be customized depending upon the area to be treated. The distance between the embedded catheter and the surface is 0.5 cm, allowing for acceptable dose uniformity at the surgical bed surface while maximizing the dose falloff with depth.137 After tumor resection, an appropriate-sized applicator is placed on the tumor bed and secured into place with suturing and/or gauze packing (see Figs. 3.13, 3.14, 3.15, 3.16, 3.17, 3.18 and 3.19). An accurate measurement of the tumor bed is taken to determine the number of catheters, source dwell positions, and overall treatment plan. The advantages of HDR-IORT system includes increased flexibility of the applicators, allowing easier application of nearly all complex surfaces and ability to treat large fields with minimal dosimetric inhomogeneity at the junction of abutting fields; and heterogeneity of dose distribution, which creates a hot spot up to twice as large at the surface of the applicator compared with the dose at prescription depth. The dose inhomogeneity allows the greatest dose to be delivered at the surface of the tumor bed, but creates a greater dose gradient between the surface of the tumor bed and prescription depth, typically 0.5-cm deep, compared with intraoperative electron radiation therapy (IOERT).132 Because of this dose inhomogeneity, HDR-IORT is best for “at risk” tumor beds between 0.5- and 1.0-cm thick.138

Figure 3.13 Harrison-Anderson-Mick applicators with 12 channels and 3 channels. The three-channel applicator is connected to the attachable transfer tubes.

Figure 3.14 Intraoperative high dose rate brachytherapy setup after gross total resection of recurrent parotid malignancy with prior radiation therapy. The Harrison-Anderson-Mick (HAM) applicator with six channels is in place secured by sutures and wet lap pads. Transfer tubes from the Nucletron remote afterloader unit are connected to the catheters from the HAM applicator.


Figure 3.15 An adjacent room with the computer console controlling the remote afterloading device.

Figure 3.16 A patient with a neck dissection for isolated large nodal recurrence. Note the lead shields that are placed, sparing the adjacent skin and soft tissues.


Figure 3.17 A seven-channel Harrison-Anderson-Mick applicator is placed over the tumor bed.

Figure 3.18 The Harrison-Anderson-Mick applicator is secured with sutures and numerous wet lap pads.


Figure 3.19 The Harrison-Anderson-Mick applicator is connected to the transfer tubes. These transfer tubes are then connected to the afterloader unit.


Hu et al. evaluated the use of IORT using HDR 192Ir source in 15 patients with locally advanced or recurrent head and neck cancer.139 Using a HAM applicator, a median dose of 12 Gy was delivered to the tumor bed. At a median follow-up of 10 months, the crude local control was 80% with a disease-free survival of 74%. Nag et al. analyzed the results of 29 patients with base of skull involvement.140 Six patients had previously received EBRT. Patients underwent a maximal surgical resection followed by 7.5 to 15 Gy through HDR-IORT. Local control and overall survival rates were 66% and 72%, respectively.

Garrett et al. treated 28 patients with recurrent or advanced disease after surgical resection with IOERT, where 61% of patients had undergone prior EBRT.141Local control and overall survival rates were 66% and 67%, respectively. In this group of patients, 23% also had gross residual disease following maximal surgery. Rate et al. delivered a median dose of 20 Gy using IOERT to 47 patients with recurrent previously irradiated head and neck cancer.142 Local control rate was 62%. A study by Coleman et al. also yielded similar results.143 Toita et al. also found high incidence of toxicities with doses >20 Gy with no benefit for gross residual disease.144 Pinheiro et al. concluded that IORT at a dose of 12.5 Gy is safe and produces tumor control and survival for patients likely to have microscopic residual disease in sites difficult to resect such as the skull base. Nag et al. found that use of IOERT alone, mostly with doses of 15 Gy for close/microscopically positive margin, for previously irradiated tumors after surgical resection did not provide adequate tumor control.145 The authors also found improvements in local control and overall survival when EBRT is given with HDR-IORT.146


Management of patients with head and neck cancer continues to be a challenging and evolving field filled with numerous and complex issues that necessitates a multidisciplinary approach. Such a team approach will help attain the optimal treatment strategy for patients with head and neck cancer. Brachytherapy has been shown to be an integral part of organ preservation and improvement in the quality of life, with the best functional, emotional, and cosmetic outcome. In addition, brachytherapy provides an avenue to achieve high therapeutic radiation doses for patients with recurrent or persistent head and neck cancers with prior RT. With the evolution in technology and clinical application, the use of HDR and PDR appears to be promising with their own unique advantages. However, this still remains to be seen. IORT has come a long way from its first reported application in 1905 in Spain,133 but many of the basic concepts are still the same. Also, with improvements in radiation delivery planning systems, such as with IMRT, the role of brachytherapy has been challenged. However, it is too early to effectively compare outcomes with brachytherapy, which has a much longer proven history. Brachytherapy in a head and neck cancer center continues to provide an important vital approach to help obtain the best functional and overall treatment outcome.


Chapter 3 Case Studies: Clinical Examples of Custom High dose rate Surface Applicators for Head and Neck Sites

Case 1

A large angiosarcoma with clinical target for RT on vertex of scalp in an elderly male. A custom mold with modified Aquaplast facemask material and fitted with Freiburg Flap (FF) catheters was applied to target area. CT-optimized treatment plan was developed to deliver a highly conformal surface dose of 51 Gy in 17 daily fractions (see Figs. and 3.23).

Case 2

A small angiosarcoma of right cheek with positive margins in an elderly male. A custom modified Aquaplast facemask was fitted with FF catheters similar to Case 1 in the preceding text. Lead eye shielding was used. The clinical target was defined to be 5 cm from the scar in all directions without encroaching on the eye. This took the clinical target areas up onto the nose and onto the eyelid. Dental rolls were employed at planning and during daily treatments to lift the cheek off the teeth and gingival. CT-optimized treatment plan was developed to deliver a highly conformal surface dose of 51 Gy in 17 daily fractions (see Figs. and 3.29).

Case 3

A young man with localized lip sarcoma with marginal resection. The patient received 50 Gy conformal EBRT to primary site followed by HDR surface applicator boost to lower lip. The modified mask set up with bite block and dental rolls was used for planning and for daily treatments. Freeburg Flap catheters were fixed to the mask (see Figs. 3.303.31 and 3.32).

Figure 3.20 The patient was set up in a comfortable position. The clinical target was marked out with ink and computed tomography marker wire was applied.


Figure 3.21 Additional layer of Aquaplast material is applied for maintaining stability and distance.

Figure 3.22 Additional strips of Aquaplast material hold the Freiburg Flap catheters in place.


Figure 3.23 Computed tomography–based computer optimization created a highly conformal 100% isodose distribution to the entire clinical target surface area.

Figure 3.24 The patient was placed in a comfortable supine position with a headcup. The scar and clinical target area were marked with ink and computed tomography scan marker wire. The lead eyeshield was fitted.


Figure 3.25 The Aquaplast facemask is molded and, while it is still warm and translucent, the clinical target area is inked on the new top layer.

Figure 3.26 An extra layer of Aquaplast material was added for maintaining the distance and stability of applicator. Again the target was inked on the new top layer.


Figure 3.27 The Freiburg Flap catheters were positioned to cover the clinical target area, fixed in place with extra strips and manually held as the strips get set.

Figure 3.28 The setting up of the applicator was completed and copper wire dummy strands were placed in the Freiburg Flap catheters. The catheters were uniquely numbered for the treatment plan. A noncontrasted computed tomography scan for treatment planning was obtained.


Figure 3.29 Computed tomography–based computer optimization created a highly conformal 100% isodose distribution to the entire clinical target surface area.

Case 4

A young woman with five surgeries for refractory keloid of right ear. Day of surgery treatment planning and treatment delivery to small clinical target area at inferior pole of right pinna. The surgical wound and the clinical target area were marked with CT marker wire. Wax-covered lead shielding was made for optimum normal tissue sparing, but cardboard models of the lead shields were used in the CT treatment planning (see Figs. 3.333.34 and 3.35).

Figure 3.30 A modified chinstrap facemask allowed the creation of custom biteblock and was made with dental rolls in place. Note the chin erythema and epilation from the larger first field of radiation.


Figure 3.31 Freiburg Flap catheters applied and fixed with additional strips.

Figure 3.32 Screen capture of treatment planning system showing axial computed tomography scan isodose distribution about lip with a highly conformal dose with excellent sparing of gingival mucosa. Also shown are axial, coronal, and saggital 3D graphic representations of translucent dose cloud to assist in assessment of adequacy of implant.


Figure 3.33 The clinical setup for treatment planning with molded Aquaplast applicator conformal to pinna with Freiburg Flap catheters attached. Cardboard shields are used for planning.

Figure 3.34 The clinical setup for treatment with the applicator, waxed lead, and dosimeters in place. The high dose rate afterloader transfer tubes were attached to the Freiburg Flap catheters but without touching the skin, to prevent transit dose.


Figure 3.35 Computed tomography–based computer optimized treatment plan with isodose lines conformal to small target area. This plan did not take into account extra sparing of normal tissue from waxed lead. Mosfet dosimeters verified 100% of prescription dose to clinical surface area and 7% to normal mastoid skin shielded by waxed lead.


1. Pigneux J, Richaud PM, Lagarge C. The placement of interstitial therapy using Ir-192 in the management of cancer of the lip. Cancer. 1979;43:1073–1077.

2. Lapeyre M, Bollet MA, Racodot S, et al. Postoperative brachytherapy alone and combined postoperative radiotherapy and brachytherapy boost for squamous cell carcinoma of the oral cavity, with positive or close margins. Head Neck. 2004;26(3):216–223.

3. Beitler JJ, Smith RV, Silver CE, et al. Close or positive margins after surgical resection for the head and neck cancer patient: The addition of brachytherapy improves local control. Int J Radiat Oncol Biol Phys. 1998;40:313–317.

4. Vikram B, Mishra S. Permanent iodine-125 implants in postoperative radiotherapy for head and neck cancer with positive surgical margins. Head Neck. 1994;16:155–157.

5. Looser KG, Shah JP, Strong EW. The significance of positive margins in surgically resected epidermoid carcinoma. Head Neck. 1978;1:107.

6. Fu KK, Ray JW, Chan EK, et al. External and interstitial radiation therapy of carcinomas of the oral tongue: A review of 32 years of experience. AM J Roentgenol. 1976;127:107–115.

7. Harrison LB, Ferlito A, Shaha AR, et al. Current philosophy on the management of cancer of the base of the tongue. Oral Oncol. 2003;39(2):101–105.

8. Harrison LB, Zelefsky MJ, Pfister DG, et al. Detailed quality of life assessment in patients treated with primary radiotherapy for squamous cell cancer of the base of the tongue. Head Neck. 1997;19(3):169–175.

9. Barrett WL, Gleich L, Wilson K, et al. Organ preservation with interstitial radiation for base of tongue cancer. Am J Clin Oncol. 2002;25(5):485–488.

10. Housset M, Baillet F, Dessard-Diana B, et al. A retrospective study of three treatment techniques for T1-T2 base of tongue lesions: Surgery plus postoperative radiation, external radiation plus interstitial implantation and external radiation alone. Int J Radiat Oncol Biol Phys. 1987;13(4):511–516.

11. Harrison LB, Lee HJ, Pfister DG, et al. Long term results of primary radiotherapy with/without neck dissection for squamous cell cancer of the base of tongue. Head Neck. 1998;20(8):668–673.

12. Brucer M. Brachytherapy. Am J Roentgenol. 1968;79:1080–1090.

13. Brucer M. Brachytherapy. Am J Roentgenol Radium Ther Nucl Med. 1958;79:1080–1090.

14. News and views. Nature. 2003;424(6949):627–628.

15. Wickham L, Degrais P. Radiumtherapie. Paris: Bailliere; 1909; (English ed): Radiumtherapy. London: Cassell; 1910; Radiumtherapy. New York: Funk and Wagnalis; 1910.

16. Abbe R. Radium in surgery. J Am Med Assoc. 1906;47:103.

17. Morton R. Treatment by roentgen and radium rays. Br Med J. 1904;166:941–944.

18. Minet H. Application du radium aux tumeurs vesicales, a 1'hypertophie et au cancer de la prostate. Assoc Franc Urol. 1909;13:629.

19. Khan FM. Brachytherapy. In: Pasano WM III, ed. The physics of radiation therapy, 2nd ed. Baltimore, MD: Lippincott Williams & Wilkins; 1994;418–473.

20. Paterson R, Parker HMA. A dosage system for gamma ray therapy. Br J Radiol. 1934;7:592–612.

21. Quimby EQ. Dosage tables for linear radium sources. Radiology. 1944;43:572.

22. Quimby EQ. The grouping of radium tubes in packs on plaques to produce the desired distribution of radiation. Am J Roengenol. 1932;27:18.

23. Glasser O, Quimby EH, Taylor LS, et al. Physical foundations of radiology, 3rd ed. New York: Harper & Row; 1961.

24. Pierquin B, Dutreix A, Paine C. The Paris system in interstitial radiation therapy. Acta Radiol Oncol. 1978;13:33.

25. Pierquin B, Wilson JF, Chassagne D. Modern brachytherapy. New York: Masson; 1987.

26. Henschke UK. Afterloading applicator for radiation therapy of carcinoma of the uterus. Radiology. 1960;74:834.

27. Henschke U, Hilaris BS, Mahan GD. Afterloading in interstitial and intracavitary radiation therapy. Am J Roentgenol. 1963;90:386–395.

28. Pernot M, Luporsi E, Hoffstetter S, et al. Complications following definitive irradiation for cancers of the oral cavity and the oropharynx (in a series of 1134 patients). Int J Radiat Oncol Biol Phys. 1997;37:577–585.

29. Piro JD, Battle LW, Harrison LB. Conversion of complete dentures to a radiation shield prosthesis. J Prosthet Dent. 1991;65:731–732.

30. Clarke DH, Edmundson GK, Martinez A, et al. The utilization of I#125 seeds as a substitute for Ir-192 seeds in temporary interstitial implants: An overview and a description of the William Beaumont Hospital technique. Int J Radiat Oncol Biol Phys. 1988;15(4):1027–1033.

31. Pierquin B, Marinello G. Palatal tonsillar region. In: Wilson F, ed. A practical manual of brachytherapy. Madison: Medical Physics Publishing; 1997:108–109.

32. Harrison LN, Zelefsky MJ, Sessions RB, et al. Base-of-tongue cancer treated with external beam irradiation plus brachytherapy: Oncologic and functional outcome. Radiology. 1992;184(1):267–270.

33. Gibbs IC, Le QT, Shah RD, et al. Long—term outcomes after external beam irradiation and brachytherapy boost for base-of-tongue cancer. Int J Radiat Oncol Biol Phys. 2003;57(2):489–494.

34. International commission on radiation units and measurements, dose and volume specification for reporting intracavitary therapy in gynecology. ICRU Report 38, Bethesda, USA: 1985.

35. Lau HY, Hay JH, Flores AD, et al. Seven fractions of twice daily high dose-rate brachytherapy for node-negative carcinoma of the mobile tongue results in loss of therapeutic ratio. Radiother Oncol. 1996;39:15–18.

36. Leung TW, Wong VY, Kwan KH, et al. High dose rate brachytherapy for early stage oral tongue cancer. Head Neck. 2002;24:274–278.

37. Levendag PC, Lagerwaard FJ, Noever I, et al. Role of endocavitary brachytherapy with or without chemotherapy in cancer o the nasopharynx. Int J Radiat Oncol Biol Phys. 2002;52:755–768.

38. Inoue T, Inoue T, Teshima T, et al. Phase III trial of high and low dose rate interstitial radiotherapy for early oral tongue cancer. Int J Radiat Oncol Biol Phys. 1996;36(5):1201–1204.

39. Pellizzon AC, dos Santos Novaes PE, Conte Maia MA, et al. Interstitial high-dose rate brachytherapy combined with cervical dissection on head and neck cancer. Head Neck. 2005;27(12):1035–1041.

40. Kakimoto N, Inoue T, Inoue T, et al. Results of low- and high-dose-rate interstitial brachytherapy or T3 mobile tongue cancer. Radiother Oncol. 2003;68(2):123–128.

41. Levendag PC, Schmitz PIM, Jansen PP, et al. Fractionated high dose rate and pulsed dose rate brachytherapy: First clinical experience in squamous cell carcinoma of the tonsillar fossa and soft palate. Int J Radiat Oncol Biol Phys. 1997;38(3):497–506.

42. Strnad V, Lotter M, Grabenbauer G, et al. Early results of pulsed-dose-rate interstitial brachytherapy for head and neck malignancies after limited surgery. Int J Radiat Oncol Biol Phys. 2000;46(1):27–30.

43. Peiffert D, Castelain B, Thomas L, et al. Pulsed dose rate brachytherapy in head and neck cancers. Feasibility study of a French cooperative group. Radiother Oncol. 2001;58:71–75.

44. Strnad V, Melzner W, Geiger M, et al. Role of interstitial PDR brachytherapy in the treatment of oral and oropharyngeal cancer. A single-institute experience of 236 patients. Strahlenther Onkol. 2005;181(12):762–767.

45. Strand V, Geiger M, Lotter M, et al. The role of pulsed-dose-rate brachytherapy in previously irradiated head-and-neck cancer. Brachytherapy. 2002;1(3):149–153.

46. Brenner DJ, Hall EJ. Conditions for the equivalence of continuous to pulsed low dose rate brachytherapy. Int J Radiat Oncol Biol Phys. 1991;20(1):181–190.

47. Fowler J, Mount M. Pulsed brachytherapy: The conditions for no significant loss of therapeutic ratio compared with traditional low dose rate brachytherapy. Int J Radiat Oncol Biol Phys. 1992;23(3):661–669.

48. Brenner DJ, Hall EJ, Huang Y, et al. Optimizing the time course of brachytherapy and other accelerated radiotherapeutic protocols. Int J Radiat Oncol Biol Phys. 1994;29(4):893–901.

49. Visser AG, van den Aardweg GJ, Levendag PC. Pulsed dose rate and fractionated high dose rate brachytherapy: Choice of brachytherapy schedules to low dose rate treatments. Int J Radiat Oncol Biol Phys. 1996;34(2):497–505.

50. Harrison LB, Zelefsky MJ, Armstrong JG, et al. Brachytherapy and function preservation in the localized management of soft tissue sarcomas of the extremity. Semin Radiat Oncol. 1993;3:260–269.

51. Al-Sarraf M, LeBlanc M, Giri PG, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: Phase III randomized Intergroup study 0099. J Clin Oncol. 1998;16:1310–1317.

52. Wang CC, Busse J, Gitterman M. A simple afterloading applicator for intracavitary irradiation of carcinoma of the nasopharynx. Radiology. 1975;115:737–738.

53. Teo PM, Kwan WH, Yu P, et al. A retrospective study of the role of intracavitary brachytherapy and prognostic factors determining local tumor control after primary radical radiotherapy in 903 non-disseminated nasopharyngeal carcinoma patients. Clin Oncol (R Coll Radiol). 1996;8:160–166.

54. Harrison LB, Weissberg JB. A technique for interstitial nasopharyngeal brachytherapy. Int J Radiat Oncol Biol Phys. 1987;13(3):451–453.

55. Harrison LB, Nori D, Hilaris B, et al. Nasopharynx In: The Interstitial Collaborative Working Group, eds. Interstitial brachytherapy. New York: Raven Press; 1990:95–109.

56. Vikram B, Hilaris B. Transnasal permanent interstitial implantation of carcinoma of the nasopharynx. Int J Radiat Oncol Biol Phys. 1984;10:153–155.

57. Fu KK, Newman H, Phillips TL. Treatment of locally recurrent carcinoma of the nasopharynx. Radiology. 1975;117(2):425–431.

58. Wang CC. Improved local control of nasopharyngeal carcinoma after intracavitary brachytherapy boost. Am J Clin Oncol. 1998;14:5–8.

59. Harrison LB, Sessions RB, Fass DE, et al. Nasopharyngeal brachytherapy with access via a transpalatal flap. Am J Surg. 1992;164(2):173–175.

60. Jorgensen K, Elbronad O, Anderson AP. Carcinoma of the lip. A series of 869 cases. Acta Radiol Ther Phys Biol. 1973;12:177–190.

61. Harrison LB, Nori D, Hilaris BS, et al. Nasopharynx In: Interstitial Collaborative Working Group. eds. Interstitial brachytherapy. New York: Raven Press; 1990:95–109.

62. Syed AM, Puthawala AA, Damore SJ, et al. Brachytherapy for primary and recurrent and nasopharyngeal carcinoma: 20 years' experience at Long Beach Memorial. Int J Radiat Oncol Biol Phys. 2000;47:1311–1321.

63. Pryzant RM, Wendt CD, Delclos L, et al. Re-treatment of nasopharyngeal carcinoma in 53 patients. Int J Radiat Oncol Biol phys. 1992;22:941–947.

64. Lee AW, Law SC, Foo W, et al. Retrospective analysis of patients with nasopharyngeal carcinoma treated during 1976–1985: Survival after local recurrence [see comments]. Int J Radiat Oncol Biol Phys. 1993;26:773–782.

65. Kwong DL, Wei WI, Chen AC, et al. Long term results of radioactive gold grain implantation for the treatment of persistent and recurrent nasopharyngeal carcinoma. Cancer. 2001;91:1105–1113.

66. Wang CC. Re-irradiation of recurrent nasopharyngeal carcinoma-treatment techniques and results. Int J Radiat Oncol Biol Pys. 1987;13:953–956.

67. Choy D, Sham JST, Wei WI, et al. Transpalatal insertion of radioactive gold grain for the treatment of persistent and recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 1993;25:505–512.

68. Heller KS, Shah JP. Carcinoma of the lip. Am J Surg. 1979;138:600–609.

69. Decroix Y, Ghossein NA. Experience of the Curie Institute in treatment of cancer of the mobile tongue: Treatment policies and results. Cancer. 1981;47:496–502.

70. Mazeron JJ, Crook JM, Benck V, et al. Iridium 192 implantation of T1 and T2 carcinomas of the mobile tongue. Int J Radiat Oncol Biol Phys. 1990;19:1369–1376.

71. Spiro RH, Strong EW. Epidermoid carcinoma of the mobile tongue. Treatment by partial glossectomy alone. Am J Surg. 1971;122:707–710.

72. Ange DW, Lindberg RD, Guillamondegui OM. Management of squamous cell carcinoma of the oral tongue and floor of mouth after excisional biopsy. Radiology. 1975;116:143–146.

73. Mendenhall WM, Parsons JT, Stringer SP, et al. Radiotherapy after excisional biopsy of carcinoma of the oral tongue/floor of mouth. Head Neck. 1989;11:129–131.

74. Brown M, Hu K, Harrison L. Adjuvant interstitial brachytherapy for resected T1 and T2 cancer of the oral cavity with close or positive margins. American brachytherapy annual meeting society proceedings. Vancouver, British Columbia; 2001:69.

75. Chu A, Fletcher GH. Incidences and causes of failure to control by irradiation the primary lesion in squamous cell carcinomas of the anterior two thirds of the tongue and floor of mouth. Am J Roentgenol. 1973;117:502–508.

76. Pernot M, Hoffstetter S, Peiffert D, et al. Epidermoid carcinomas of the floor of mouth treated by exclusive irradiation: Statistical study of a series of 207 cases. Radiother Oncol. 1995;35(3):177–185.

77. Mazeron JJ, Grimard L, Raynal M, et al. Iridium-192 curietherapy for T1 and T2 epidermoid carcinomas of the floor of mouth. Int J Radiat Oncol Biol Phys. 1990;18(6):1299–1306.

78. Matsumoto S, Takeda M, Shibuya H, et al. T1 and T2 squamous cell carcinomas of the floor of the mouth: Results of brachytherapy mainly using 198Au grains. Int J Radiat Oncol Biol Phys. 1996;34(4):833–841.

79. Marsiglia H, Haie-Meder C, Sasso G, et al. Brachytherapy for T1-T2 floor-of-the-mouth cancers: The Gustave-Roussy Institute experience. Int J Radiat Oncol Biol Phys. 2002;52(5):1257–1263.

80. Morrish RB Jr, Chan E, Silverman S Jr, et al. Osteonecrosis in patients irradiated for head and neck carcinoma. Cancer. 1981;47(8):1980–1983.

81. Beumer J, Harrison R, Sanders B, et al. Osteoradionecrosis: Predisposing factors and outcomes of therapy. Head Neck Surg. 1984;6(4):819–827.

82. Jeng JH, Chang MC, Hahn LJ. Role of areca nut in betel quid-associated chemical carcinogenesis: Current awareness and future perspectives. Oral Oncol. 2001;37(6):477–492.

83. Merchant A, Husain SS, Hosin M, et al. Paan without tobacco: An independent risk factor for oral cancer. Int J Cancer. 2000;86(1):128–131.

84. Lapeyre M, Peiffert D, Mallissard L, et al. An original technique of brachytherapy in the treatment of epidermoid carcinomas of buccal mucosa. Int J Radiat Oncol Biol Phys. 1995;33:447–454.

85. Gerbaulet A, Pernot A. Cancer of the buccal mucosa-proceedings of the 20th annual meeting of the European Curietherapy Group. J Eur Radiother. 1985;6:1–4.

86. Nair MK, Sankaranarayanan R, Padmanabhan TK. Evaluation of the role of radiotherapy in the management of carcinoma of the buccal mucosa. Cancer. 1988;61(7):1326–1331.

87. Lindberg R. Distribution of cervical lymph node metastases from squamous cell carcinoma of the upper respiratory and digestive tracts. Cancer. 1972;29(6):1446–1449.

88. Kraus DH, Vastola AP, Huvos AG, et al. Surgical management of squamous cell carcinoma of the base of the tongue. Am J Surg. 1993;166(4):384–388.

89. Machtay M, Perch S, Markiewicz D, et al. Combined surgery and postoperative radiotherapy for carcinoma of the base of radiotherapy for carcinoma of the base of tongue: Analysis of treatment outcome and prognostic value of margin status. Head Neck. 1997;19(6):494–499.

90. Mendenhall WM, Stringer SP, Amdur RJ, et al. Is radiation therapy a preferred alternative to surgery for squamous cell carcinoma of the base of tongue? J Clin Oncol. 2000;18(1):35–42.

91. Jaulerry C, Rodriguez J, Brunin F, et al. Results of radiation therapy in carcinoma of the base of the tongue. The Curie Institute experience with about 166 cases. Cancer. 1991;67(6):1532–1538.

92. Horwitz EM, Frazier AJ, Martinez AA, et al. Excellent functional outcome in patients with squamous cell carcinoma of the base of tongue treated with external irradiation and interstitial iodine 125 boost. Cancer. 1996;78(5):948–957.

93. Crook J, Mazeron J, Marinello G, et al. Combined external irradiation and interstitial implantation for T1 and T2 epidermoid carcinomas of base of tongue: The Creteil experience (1971–1981). Int J Radiat Oncol Biol Phys. 1988;15:105–114.

94. Goffinet DR, Fee WE Jr, Wells J, et al. 192Ir pharyngoepiglottic fold interstitial implants. The key to successful treatment of base tongue carcinoma by radiation therapy. Cancer. 1985;55(5):941–948.

95. Gibbs I, Le Q, Shah R, et al. Long-term outcomes after external beam irradiation and brachytherapy boost for base-of-tongue cancers. Int J Radiat Oncol Biol Phys. 2003;57(2):489–494.

96. Hoffstetter S, Marchal C, Peiffert D, et al. Treatment duration as a prognostic factor for local control and survival in epidermoid carcinomas of the tonsillar region treated by combined external beam irradiation and brachytherapy. Radiother Oncol. 1997;45:141–148.

97. Puthawala AA, Syed AM, Eads DL, et al. Limited external beam and interstitial 192iridium irradiation in the treatment of carcinoma of the base of the tongue: A ten year experience. Int J Radiat Oncol Biol Phys. 1988;14(5):839–848.

98. Horwitz PEM, Harris J, Langer CJ, et al. Phase II Study of paclitaxel and cisplatin in combination with split course concomitant hyperfractionated re-irradiation in patients with recurrent squamous cell cancer of the head and neck: Results of RTOG 99-11. Int J Radiat Oncol Biol Phys. 2005;63(S1):S72–S73.

99. Harrison LB, Zelefsky MJ, Armstrong JG, et al. Performance status after treatment for squamous cell cancer of the base of tongue—a comparison of primary radiation therapy versus primary surgery. Int J Radiat Oncol Biol Phys. 1994;30(4):953–957.

100. Regueiro CA, Millan I, de la Torre A, et al. Influence of boost technique (external beam radiotherapy or brachytherapy) on the outcome of patients with carcinoma of the base of tongue. Acta Oncol. 1995;34:225–233.

101. Han P, Hu K, Culliney B, et al. Concurrent chemoradiation followed by interstitial brachytherapy boost and neck dissection for T4 base of tongue cancer. Int J Radiat Oncol Biol Phys. 2005;63(S1):S358.

102. List MA, Ritter-Sterr C, Lansky SB. A performance status scale for head and neck cancer patients. Cancer. 1990;66(3):564–569.

103. Jesse RH Jr, Fletcher GH. Metastases in cervical lymph nodes from oropharyngeal cancer: Treatment and results. Am J Roentgenol. 1963;90:990–996.

104. Pierquin B, Marinello G. Palatal tonsillar. In: Wilson F, ed. A practical manual of brachytherapy. Madison: Medical Physics Publishing; 1997:138–146.

105. Pernot M, Malissard L, Hoffstetter S, et al. Influence of tumoral, radiobiological and general health factors on local control and survival of a series of 361 tumors of the velotonsillar area treated by exclusive irradiation (external beam + brachytherapy or brachytherapy alone). Int J Radiat Oncol Biol Phys. 1994;30:1021–1027.

106. Mazeron JJ, Belkacemi Y, Simon JM, et al. Place of iridium 192 implantation in definitive irradiation of faucial arch squamous cell carcinomas. Int J Radiat Oncol Biol Phys. 1993;27:251–257.

107. Behar RA, Martin PJ, Fee WE Jr, et al. Iridium-192 interstitial implant and external beam radiation therapy in the management of squamous cell carcinomas of the tonsil and soft palate. Int J Radiat Oncol Biol Phys. 1994;28:221–227.

108. Mazeron JJ, Marinello G, Crook J, et al. Definitive radiation treatment for early stage carcinoma of the soft palate and uvula: The indications for iridium 192 implantation. Int J Radiat Oncol Biol Phys. 1987;13:1829–1837.

109. Puthawala AA, Syed AM, Gates TC. Iridium-192 implants in the treatment of tonsillar region malignancies. Arch Otolaryngol. 1985;111:812–815.

110. Garrett PG, Beale FA, Cummings BJ, et al. Carcinoma of the tonsil: The effect of dose-time-volume factors on local control. Int J Radiat Oncol Biol Phys. 1985;11:703–706.

111. Amornmarn R, Prempree T, Jaiwatana J, et al. Radiation management of carcinoma of the tonsillar region. Cancer. 1984;54(7):1293–1299.

112. Spencer SA, Harris J, Wheeler RH, et al. RTOG 96-10: Reirradiation with concurrent hydroxyurea and 5-fluorouracil in patients with squamous cell cancer of the head and neck. Int J Radiat Oncol Biol Phys. 2001;51(5):1299–1304.

113. Spencer S, Harris J, Wheeler R, et al. Late effects of RTOG-9610: Re-irradiation and chemotherapy in patients with squamous cell cancer of the head and neck. Int J Radiat Oncol Biol Phys. 2003;57(2, S1):S307.

114. Milano MT, Vokes EE, Salama JK, et al. Twice-daily reirradiation for recurrent and second primary head-and-neck cancer with gemcitabine, paclitaxel, and 5-fluorouracil chemotherapy. Int J Radiat Oncol Biol Phys. 2005;61(4):1096–1106.

115. Kramer NM, Horwitz EM, Cheng J, et al. Toxicity and outcome analysis of patients with recurrent head and neck cancer treated with hyperfractionated split-course reirradiation and concurrent cisplatin and paclitaxel chemotherapy from two prospective phase I and II studies. Head Neck. 2005;27(5):406–414.

116. Kao J, Garofalo MC, Milano MT, et al. Reirradiation of recurrent and second primary head and neck malignancies: A comprehensive review. Cancer Treat Rev. 2003;29(1):21–30.

117. Stafford N, Dearnaley D. Treatment of ‘inoperable’ neck nodes using surgical clearance and postoperative interstitial irradiation. Br J Surg. 1988;75:62–64.

118. Moscoso JF, Urken ML, Dalton J, et al. Simultaneous interstitial radiotherapy with regional or free-flap reconstruction, following salvage surgery of recurrent head and neck carcinoma. Analysis of complications. Arch Otolaryngol Head Neck Surg. 1994;120:965–972.

119. Anderson LL. A spacing nomograph for interstitial implants of 125-I seeds. Med Phys. 1976;3:48.

120. Goffinet DR, Martinez A, Fee WE. I-125 vicryl suture implants as a surgical adjuvant in cancer of the head and neck. Int J Radiat Oncol Biol Phys. 1985;11:399–402.

121. Choo R, Grimard L, Esche B, et al. Brachytherapy of neck metastases. J Otolaryngol. 1993;22(1):54–57.

122. Cornes PG, Cox HJ, Rhys-Evans PR, et al. Salvage treatment for inoperable neck nodes in head and neck cancer using combined iridium-192 brachytherapy and surgical reconstruction. Br J Surg. 1996;83(11):1620–1622.

123. Bollet MA, Lapeyre M, Marchal C, et al. Cervical lymph node relapses of head-and-neck squamous cell carcinoma: Is brachytherapy a therapeutic option? Int J Radiat Oncol Biol Phys. 2001;51(5):1305–1312.

124. Puthawala A, Nisar Syed AM, Gamie S, et al. Interstitial low-dose-rate brachytherapy as a salvage treatment for recurrent head-and-neck cancers: Long-term results. Int J Radiat Oncol Biol Phys. 2001;51(2):354–362.

125. Peiffert D, Pernot M, Malissard L, et al. Salvage irradiation by brachytherapy of velotonsillar squamous cell carcinoma in a previously irradiated field: Results in 73 cases. Int J Radiat Oncol Biol Phys. 1994;29:681–686.

126. Mazeron JJ, Langlois D, Glaubiger D, et al. Salvage irradiation of oropharyngeal cancers using Iridium 192 wire implants: 5-year results of 70 cases. Int J Radiat Oncol Biol Phys. 1987;13:957–962.

127. Stevens KR Jr, Britsch A, Moss WT. High-dose reirradiation of head and neck cancer with curative intent. Int J Radiat Oncol Biol Phys. 1994;29:687–698.

128. Park RI, Liberman FZ, Lee DJ, et al. Iodine-125 seed implantation as an adjunct to surgery in advanced recurrent squamous cell cancer of the head and neck. Laryngoscope. 1991;101(4 Pt 1):405–410.

129. Leung TW, Tung SY, Wong VY, et al. Salvage radiation therapy for locally recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2000;48(5):1331–1338.

130. Hepel JT, Syed AM, Puthawala A, et al. Salvage high-dose-rate (HDR) brachytherapy for recurrent head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2005;62(5):1444–1450.

131. Nag S, et al. Intraoperative irradiation with electron-beam or high-dose-dose brachytherapy. In: Gunderson L, Willett CG, Harrison LB, et al. eds. Intraoperative irradiation. Totowa, NJ: Humana Press; 1999:111–130.

132. Medina R, Casas F, Calvo FA. Radiation oncology in Spain: Historical notes for the radiology centennial. Int J Radiat Oncol Biol Phys. 1996;35:1075–1097.

133. Comas C, Prio A. Irradiation roentgen preventive intraabdominale, apres l'intervention chirurgicable dans un cas de cancer de l' uterus. Communication an III an. Congres International d'Electrologie 1906. Barcelona: Imprenta Francisco Badia; 1907:5–14.

134. Beck C. Uber Kombinationsbehandlung bei bosartigen neubildungen. Berl Klin Wochenschr. 1907;44:1335.

135. Dobelbower RR, Abe M. Intraoperative radiation therapy. Boca Raton, FL: CRC Press; 1989.

136. Sabbas AM, Kulidzhanov FG, Presser J, et al. HDR brachytherapy with surface applicators: Technical considerations and dosimetry. Technol Cancer Res Treat. 2004;3(3):259–267.

137. Harrison LB, Cohen AM, Enker WE. High-dose-rate intraoperative irradiation (HDR-IORT). In: Gunderson L, Willett CG, Harrison LB, et al. eds. Intraoperative irradiation. Totowa, NJ: Humana Press; 1999:105–110.

138. Hu KS, Enker WE, Harrison LB. High-dose-rate intraoperative irradiation: Current status and future directions. Semin Radiat Oncol. 2002;12(1):62–80.

139. Nag S, Schuller D, Pak V, et al. Pilot study of intraoperative high dose rate brachytherapy for head and neck cancer. Radiother Oncol. 1996;41(2):125–130.

140. Garrett P, Pugh N, Ross D, et al. Intra-operative radiation therapy for advanced or recurrent head and neck cancer. Int J Radiat Oncol Biol Phys. 1987;13(5):785–788.

141. Rate WR, Garrett P, Hamaker R, et al. Intraoperative radiation therapy for recurrent head and neck cancer. Cancer. 1991;67(11):2738–2740.

142. Coleman CW, Roach M III, Ling SM, et al. Adjuvant electron-beam IORT in high-risk head and neck cancer patients. Front Radiat Ther Oncol. 1997;31:105–111.

143. Toita T, Nakano M, Takizawa Y, et al. Intraoperative radiation therapy (IORT) for head and neck cancer. Int J Radiat Oncol Biol Phys. 1994;30(5):1219–1224.

144. Nag S, Schuller DE, Martinez-Monge R, et al. Intraoperative electron beam radiotherapy for previously irradiated advanced head and neck malignancies. Int J Radiat Oncol Biol Phys. 1998;42(5):1085–1089.

145. Nag S, Koc M, Schuller DE, et al. Intraoperative single fraction high-dose-rate brachytherapy for head and neck cancers. Brachytherapy. 2005;4(3):217–223.

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